Variations in disease burden of laryngeal cancer attributable to alcohol use and smoking in 204 countries or territories, 1990-2019.

BACKGROUND: Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. METHODS: Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. RESULTS: Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41-1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. CONCLUSION: The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

Analysis of subjective perception and influencing factors of different inclusive education models among prelingually deaf children with a cochlear implant.

OBJECTIVE: We aimed to explore the educational outcome and influencing factors of ongoing verbal rehabilitation training together with inclusive education among prelingually deaf children with a cochlear implant. METHODS: Prelingually deaf children who underwent cochlear implantation, rehabilitation, and had inclusive education placement were randomly divided into two groups: one group received continuous verbal rehabilitation training under inclusive education status; the other group did not receive this training. Speech discrimination scores were determined. RESULTS: Among 60 included children, subjectively perceived academic adaptability, peer relations, initiative communication, and teacher's involvement under inclusive education, as well as speech discrimination scores, were all significantly different between groups. Continuous verbal rehabilitation training influenced the subjective perception of children and resulted in higher speech discrimination scores and more positive subjective perception. Subjective perception was not significantly correlated with chronological age, sex, age at the time of cochlear implantation, or duration of inclusive education. CONCLUSION: Ongoing verbal rehabilitation training within inclusive education can largely improve the education placement outcomes of prelingually deaf children with cochlear implants.

Cervical vestibular evoked myogenic potential testing for assessment of vestibular functions in cochlear implant patients.

This study aims to investigate the vestibular function status of cochlear implant patients using cervical vestibular evoked myogenic potential (cVEMP) testing and estimate the effects of cochlear implants on vestibular function. The cVEMPs of 50 cochlear implant patients were measured preoperatively, and at one and six months postoperatively. Then, implanted ears and non-implanted ears were compared in terms of p13/n23 wave response rates, latency, amplitude and threshold. Preoperatively, the binaural cVEMP response rate was 92%, while the cVEMP response rates of implanted ears vs. non-implanted ears at postoperative one and six months were 24% vs. 80% and 52% vs. 82%, respectively. No significant difference between implanted and non-implanted ears was found preoperatively, in terms of latent period, amplitude, or threshold. However, significant changes were found in amplitude and threshold for implanted ears after the operation, but not in latency. No significant postoperative change was found in amplitude, latent period, or threshold for non-implanted ears. Significant differences between implanted and non-implanted ears were found in both amplitude and threshold. Cochlear implants affect vestibular function, especially saccular function, and reduce the cVEMP amplitude and threshold of implanted ears.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Sudden Sensorineural Hearing Loss.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is a common acute disease with an incidence of 0.5-2/10,000. This study aimed to determine whether the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) could be indicators for SSNHL. METHODS: A total of 60 confirmed cases of SSNHL and 60 healthy volunteers were included in this study. Peripheral blood NLRs and PLRs were compared between these groups. The SSNHL patients were divided into two groups, according to therapeutic effect: an effective group and an ineffective group. Peripheral blood NLRs and PLRs before and after treatment were compared between these two groups. RESULTS: The average NLRs and PLRs of these patients were both significantly higher than in controls. The average NLRs and PLRs of the ineffective group were both significantly higher than those of the effective group. CONCLUSION: Peripheral blood NLR and PLR could be used as a convenient, reliable, and cost-effective indicator to predict the prognosis of SSNHL.

Correlation between Preoperative Auditory Steady-State Response and Postoperative Electrically Evoked Auditory Brainstem Response and T Level in Cochlear Implantation for Child Patients with Inner-Ear Malformations.

OBJECTIVE: This study aims to investigate the correlation between thresholds of preoperative multiple auditory steady-state response (ASSR) and electrically evoked auditory brainstem response (EABR) and the behavioral threshold. METHODS: A total of 72 patients were elected to receive a multichannel cochlear implant. According to the residual hearing determined in a preoperative test using high-, moderate-, and low-frequency ASSR, these patients were divided into the following 2 groups: residual hearing and hearing loss. The EABR and behavioral thresholds 1 year after implantation were assayed, and differences between these 2 parameters were compared. RESULTS: Among the high-, moderate-, and low-frequency residual hearing groups, the EABR and behavioral thresholds of patients 1 year after implantation were significantly lower than those in the hearing loss group, and the differences were statistically significant (p < 0.01). CONCLUSION: Before the operation, ASSR results can be used to predict the efficacy of cochlear implantation in patients, and they serve as one of the reference conditions for choosing the ear for implantation. However, the threshold of ASSR is not equivalent to the actual auditory threshold of patients after implantation, and the deviation between these 2 thresholds is more significant at low frequencies.

Postoperative objective detecting techniques for cochlear implant children with inner ear malformation.

OBJECTIVES: This study aims to investigate the changing characteristics and rules of electrically-evoked auditory brainstem response (EABR), electrically-evoked stapedius reflex threshold (ESRT) and neural response telemetry (NRT) after cochlear implant in children with inner ear malformation, and guide postoperative equipment debug. METHODS: A total of 88 children with either normal cochlea (control group) or inner ear malformation (test group) received Australian 24 multi-channel cochlear implants. The EABR, ESRT and NRT thresholds at different time points within one year postoperatively and behavioral responses (T-level and C-level) after one year were detected. Furthermore, the changing characteristics and rules of these thresholds were analyzed. RESULTS: The EABR, ESRT and NRT thresholds were all significantly higher at all time points in the test group than in the control group, but the general changing trends were similar. Particularly, these thresholds worsened at low frequencies and improved at high frequencies. Furthermore, EABR, ESRT and NRT thresholds gradually increased during the one year postoperative period. In addition, an extremely significant correlation was found between EABR and T-level and between ESRT and C-level, but a less significant correlation was found between NRT threshold and T-level in both groups. CONCLUSIONS: The postoperative changes in characteristics and rules of EABR, ESRT and NRT thresholds among cochlear implant children with inner ear malformation were all the same as those with normal cochlea. Thus, these thresholds can be used to guide the postoperative equipment debug for cochlear implants into patients with inner ear malformation.

Staphylococcal enterotoxin B-derived haptens promote sensitization.

T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB(+) CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB(-) CRS. Ssps were detected in the stool protein extracts from FA patients with SEB(+) CRS, but not in those with SEB(-) CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4(+) T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB(+) CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.

Deficiency of ubiquitin A20 promotes antigen transport across airway epithelial cells via a transcellular pathway.

The epithelial barrier dysfunction is associated with the pathogenesis of a number of diseases. Ubiquitin E3 ligase A20 (A20) plays a critical role in maintaining the homeostasis in the body. This study aimed to investigate the role of A20 in the degradation of endocytic antigens in airway epithelial cells. The expression of A20 in the human nasal epithelial cell line, RPMI 2650 cells (Rpcs), was evaluated. The role of A20 in maintaining the intracellular permeability in Rpc monolayers was assessed in Transwells. The endosome/lysosome fusion in epithelial cells was observed by immunocytochemistry. On the absorption of antigen, the expression of A20 was increased in Rpcs. The knockdown of the A20 gene in Rpcs increased the amounts of the endocytic antigens across the Rpc monolayers. A20 was required in the process of the endosome/lysosome fusion. The antigens transported to the basal compartment by A20-deficient Rpc monolayers still kept strong antigenicity. The nasal epithelial cell line, Rpcs, expresses A20 that facilitates the degradation of endocytic antigens in Rpcs by facilitating the endosome/lysosome fusion.

Ubiquitin E3 ligase A20 facilitates processing microbial product in nasal epithelial cells.

Microbial products play a role in the pathogenesis of allergic diseases; ubiquitin E3 ligase A20 (A20) is an important molecule in regulating inflammation in the body. The present study aims to elucidate the role of A20 in processing the absorbed microbial products in nasal epithelial cells. Human nasal mucosal specimens were collected from patients with or without chronic rhinitis and analyzed by immunohistochemistry. Human nasal epithelial cell line, RPMI2650 cell, was employed to assess the role of A20 in processing the absorbed staphylococcal enterotoxin B (SEB). The RPMI2650 cells absorbed SEB in the culture. The increase in A20 was observed in RPMI2650 cells in parallel to the absorption of SEB. A20 is a critical molecule in the degradation of SEB in the nasal epithelial cells by promoting the tethering of endosomes and lysosomes. A20 plays a critical role in processing of the absorbed SEB in nasal epithelial cells.

Intestinal epithelial cell-derived integrin αß6 plays an important role in the induction of regulatory T cells and inhibits an antigen-specific Th2 response.

Toleroge nic DCs and Tregs are believed to play a critical role in oral tolerance. However, the mechanisms of the generation of tolerogenic DCs and activation of Tregs in the gut remain poorly understood. This study aims to dissect the molecular mechanisms by which IECs and protein antigen induce functional tolerogenic DCs and Tregs. Expression of αvß6 by gut epithelial cell-derived exosomes, its coupling with food antigen, and their relationship with the development of functional tolerogenic DCs and Tregs were examined by using in vitro and in vivo approaches. The results show that IECs up-regulated the integrin αvß6 upon uptake of antigens. The epithelial cell-derived exosomes entrapped and transported αvß6 and antigens to the extracellular environment. The uptake of antigens alone induced DCs to produce LTGFß, whereas exosomes carrying αvß6/antigen resulted in the production of abundant, active TGF-ß in DCs that conferred to DCs the tolerogenic properties. Furthermore, αvß6/OVA-carrying, exosome-primed DCs were found to promote the production of active TGF-ß in Tregs. Thus, in vivo administration of αvß6/OVA-laden exosomes induced the generation of Tregs and suppressed skewed Th2 responses toward food antigen in the intestine. Our study provides important molecular insights into the molecular mechanisms of Treg development by demonstrating an important role of IEC-derived exosomes carrying αvß6 and food antigen in the induction of tolerogenic DCs and antigen-specific Tregs.

Interferon-λ mediates oral tolerance and inhibits antigen-specific, T-helper 2 cell-mediated inflammation in mouse intestine.

BACKGROUND & AIMS: Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen-related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell-mediated inflammation in the intestine. METHODS: Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell-mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine. RESULTS: CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ-primed CD3+ cells inhibited Th2 cell-mediated inflammation in the intestine. CONCLUSIONS: IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell-mediated inflammation in patients.

Role of thymic stromal lymphopoietin in the pathogenesis of nasal polyposis.

INTRODUCTION: Polyposis is an end form of chronic mucosal inflammation in a number of disorders and has an important impact on patient's life quality. Thymic stromal lymphopoietin (TSLP) is involved in many inflammatory processes such as asthma and allergic rhinitis (AR). The aim of this study is to elucidate the role of TSLP in the pathogenesis of polyposis. METHODS: Ninety-four patients with nasal polyposis (NP) and/or allergic rhinitis (AR) were treated with inferior turbinectomy and polyp resection. Levels of TSLP in the nasal epithelial layer were measured; expression of TSLP receptor and OX40 ligand (OX40L) was assessed in isolated nasal mucosal dendritic cells (DC); tumor necrosis factor (TNF), interleukin (IL)-4 and interferon (IFN)-γ expressions were determined in isolated nasal mucosal CD4(+) T cells. RESULTS: The levels of TSLP in nasal epithelial layer were higher in the NP group than in the non-NP group. Higher expression of TSLP receptor and OX40L were detected in DCs of NP nasal mucosa. TNF-α(+) IL-4(+)CD4(+) T cells were detected in NP/AR nasal mucosa; TNF(+) IFN-γ(+) CD4(+) T cells were identified in NP/non-AR nasal mucosa. TSLP-primed DCs drove naive CD4(+) T cells to become TNF(+) IL-4(+) CD4(+) T cells, whereas TSLP/lipopolysaccharide-primed DCs induced naive CD4(+) T cells to become TNF(+) IFN-γ(+) T cells. CONCLUSIONS: The data indicate that TSLP is involved in the pathogenesis of polyposis.

[Expression and DNA binding activity of NF-kappaB in mucosal tissue of chronic rhinosinusitis].

OBJECTIVE: To study the expression and activation of nuclear factor-kappa B (NF-kappaB) in mucosa of rhinosinusitis. METHODS: The expressions of NF-kappaB p50 and p65 in the mucosa from 18 patients and 10 norms were detected with the method of immunohistochemistry. The activation of DNA-binding proteins which was labelled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected with electrophoretic mobility shift assays (EMSA) in mucosa. RESULTS: Plasma of epithelial and glandular cells displayed a strongly positive staining reaction to p65, and nucleus displayed a strongly positive staining reaction to p50 (7.8%-52.1%). There was significantly difference (chi2 = 22.917, P < 0.01). The DNA-binding proteins activity of 18 samples from patients with chronic rhinosinusitis (28.14 +/- 16.71) was stronger than that (9.28 +/- 2.84) in normal subjects (t = 4.56, P < 0.05). CONCLUSIONS: The expression and DNA-binding proteins activity of NF-kappaB was enhanced. It indicated that NF-kappaB was activated in mucosal inflammation of chronic rhinosinusitis.