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1.
Heliyon ; 10(9): e29933, 2024 May 15.
Article En | MEDLINE | ID: mdl-38707417

FAM83B, as one of the FAM83 family members, has been closely involved in cell transformation, and a growing number of scholars have been studied its role in tumours over the years. Whereas the effect and potential mechanism of FAM83B in laryngeal squamous cell carcinoma (LSCC) have not been investigated. In this research, we discovered that the expression quantity of FAM83B was remarkably higher in LSCC tissues (79.65 ± 35.98) than in matched adjacent tissues (59.34 ± 32.59) by tissue microarrays and immunohistochemistry. Furthermore, expression of FAM83B was knocked down in HEP-2 and TU177 cell lines via lentivirus, and in the course of intracorporal and extracorporeal experiments, FAM83B knockdown showed the inhibition of tumour growth, migration, and invasion ability. Moreover, cell cycle assay showed that FAM83B knockdown leads to an apparent accumulation of cells in the G1 phase, indicating that FAM83B knockdown can inhibit cell proliferation. Meanwhile, western blotting (WB) demonstrated that FAM83B knockdown led to a significant reduction in CDK4/CDK6/CCND1 protein expression, which may have decelerated cell cycle progression. Collectively, this study demonstrates that FAM83B serves as an oncogene in LSCC, promoting cell proliferation by controlling the protein expression of CDK4, CDK6, and CCND1, thus inducing a transference of the G1 stage to S stage in cell-cycle of LSCC cells. These results provide an academic foundation for elucidating the mechanism of LSCC occurrence and evolution and for developing treatment strategies for LSCC.

2.
Radiol Med ; 129(2): 229-238, 2024 Feb.
Article En | MEDLINE | ID: mdl-38108979

BACKGROUND: The accurate identification and evaluation of lymph nodes by CT images is of great significance for disease diagnosis, treatment, and prognosis. PURPOSE: To assess the lymph nodes' segmentation, size, and station by artificial intelligence (AI) for unenhanced chest CT images and evaluate its value in clinical scenarios. MATERIAL AND METHODS: This retrospective study proposed an end-to-end Lymph Nodes Analysis System (LNAS) consisting of three models: the Lymph Node Segmentation model (LNS), the Mediastinal Organ Segmentation model (MOS), and the Lymph Node Station Registration model (LNR). We selected a healthy chest CT image as the template image and annotated 14 lymph node station masks according to the IASLC to build the lymph node station mapping template. The exact contours and stations of the lymph nodes were annotated by two junior radiologists and reviewed by a senior radiologist. Patients aged 18 and above, who had undergone unenhanced chest CT and had at least one suspicious enlarged mediastinal lymph node in imaging reports, were included. Exclusions were patients who had thoracic surgeries in the past 2 weeks or artifacts on CT images affecting lymph node observation by radiologists. The system was trained on 6725 consecutive chest CTs that from Tianjin Medical University General Hospital, among which 6249 patients had suspicious enlarged mediastinal lymph nodes. A total of 519 consecutive chest CTs from Qilu Hospital of Shandong University (Qingdao) were used for external validation. The gold standard for each CT was determined by two radiologists and reviewed by one senior radiologist. RESULTS: The patient-level sensitivity of the LNAS system reached of 93.94% and 92.89% in internal and external test dataset, respectively. And the lesion-level sensitivity (recall) reached 89.48% and 85.97% in internal and external test dataset. For man-machine comparison, AI significantly apparently shortened the average reading time (p < 0.001) and had better lesion-level and patient-level sensitivities. CONCLUSION: AI improved the sensitivity lymph node segmentation by radiologists with an advantage in reading time.


Artificial Intelligence , Deep Learning , Humans , Retrospective Studies , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Tomography, X-Ray Computed/methods
3.
Article Zh | MEDLINE | ID: mdl-37253524

Objective:The auditory and speech rehabilitation effects were assessed by the Categories of Auditory Performance(CAP) and the speech intelligibility rating scale(SIR) after cochlear implantation(CI) in prelingually elderly patients by telephone follow-up or face-to-face conversation. Methods:The clinical data of the prelingually deaf patients who underwent unilateral CI in the Department of Otorhinolaryngology and Head and Neck Surgery, Shanxi People's Hospital, from December 2016 to December 2021 were collected. Thirty-eight patients were divided into Group A(SIR 1, 17 cases), Group B(SIR 2, 10 cases) and Group C(SIR 3, 11 cases) according to the preoperative SIR Score. Nineteen patients with post-lingual hearing impairment were selected as the control group(Group D, 19 cases). The effects of hearing and speech rehabilitation were evaluated using CAP and SIR Scores before surgery, 6 months after startup, and 1 year after startup. Results:There were no significant differences in CAP scores among the three groups of patients with prelingually deaf patients at 6 months and 1 year after startup(P>0.05), but there were significant differences between group A and group D at 6 months and 1 year after startup(P<0.05); the SIR Score of group A had statistical difference before surgery and 6 months after startup(P<0.05), group B had statistical difference before surgery and 1 year after startup(P<0.05), and group C and D had no statistical difference before surgery and 6 months and 1 year after startup, respectively(P>0.05). Conclusion:For the prelingually deaf elderly patients, hearing will develop rapidly 6 months after startup, and the effect of postoperative auditory rehabilitation was positively correlated with the preoperative speech ability. In the aspect of speech, the prelingually dear elderly patients who have poor preoperative speech ability could benefit more from CI early after surgery. CI is not contraindicated in prelingually deaf elderly patients, even those with poor preoperative speech function.


Cochlear Implantation , Cochlear Implants , Deafness , Speech Intelligibility , Humans , Cochlear Implantation/methods , Deafness/rehabilitation , Deafness/surgery , Male , Female , Aged , Aged, 80 and over , Treatment Outcome , Auditory Perception
4.
Article Zh | MEDLINE | ID: mdl-35959587

Some patients with severe-profound sensorineural hearing loss (SNHL) with normal cochlear anatomical structure received cochlear implantation (CI) and the hearing and speech rehabilitation effect was not ideal. Through retrospective analysis, it was found that some of these patients had cochlear never canal (CNC) stenosis, or atresia in severe cases.This article reviews the development of the CNC, the diagnostic criteria of CNC stenosis and the results of hearing and speech rehabilitation in these patients after CI.


Cochlear Implantation , Hearing Loss, Sensorineural , Cochlear Nerve , Constriction, Pathologic/surgery , Hearing Loss, Sensorineural/diagnosis , Humans , Retrospective Studies
6.
BMC Cancer ; 21(1): 1082, 2021 Oct 07.
Article En | MEDLINE | ID: mdl-34620148

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.


Alcohol Drinking/mortality , Cost of Illness , Global Health/statistics & numerical data , Laryngeal Neoplasms/mortality , Smoking/mortality , Alcohol Drinking/adverse effects , Cause of Death , Confidence Intervals , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Female , Humans , Laryngeal Neoplasms/etiology , Male , Mortality/trends , Risk Factors , Smoking/adverse effects , Time Factors , Tobacco Smoking/adverse effects
7.
J Int Med Res ; 48(6): 300060520929855, 2020 Jun.
Article En | MEDLINE | ID: mdl-32567996

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.


Deafness/rehabilitation , Education of Hearing Disabled/methods , Persons With Hearing Impairments/psychology , Adolescent , Auditory Perception/physiology , Child , Child, Preschool , China , Cochlear Implantation/methods , Cochlear Implants , Deafness/surgery , Education of Hearing Disabled/trends , Female , Humans , Male , Perception
8.
Eur Arch Otorhinolaryngol ; 277(9): 2447-2453, 2020 Sep.
Article En | MEDLINE | ID: mdl-32333137

OBJECTIVES: To explore the rule of extended high-frequency (EHF) audiometry recovery in patients with acute otitis media. METHODS: From January 2016 to July 2019, patients with acute otitis media in the outpatient department of otology were studied. The diagnosis was made according to the otoscopy and acoustic impedance tests, and antibiotics and other treatment programs were given. The patients were followed up to compare the effects of different recovery time on extended high-frequency audiometry in patients with acute otitis media. RESULTS: 146 patients with acute otitis media (69 in the left ear and 77 in the right ear) were selected for observation and follow-up. The patients were divided into three groups according to the time from the onset to the disappearance of hyperacusis and earache symptoms: ≤ 5 days group (26 patients, 17.8%), 6-10 days group (74 patients, 50.7%), and > 10 days group (46 patients, 31.5%). The threshold of EHF in the study group was significantly higher than that in the control group in the early stage. According to the study design for follow-up, we found that with the prolongation of the duration of acute otitis media, the extended high frequency of different groups had different changes. CONCLUSIONS: Our results show that the recovery time of EHF in patients with acute otitis media was later than that of the standard audiogram and was closely related to the course of the disease. This is of great significance for discovering the hidden hearing loss of the patients and taking the treatment plan as soon as possible.


Otitis Media with Effusion , Otitis Media , Acoustic Impedance Tests , Acute Disease , Audiometry , Audiometry, Pure-Tone , Humans , Inflammation , Otitis Media/complications , Otitis Media/diagnosis , Otoscopy
9.
Artif Organs ; 44(4): 428-434, 2020 Apr.
Article En | MEDLINE | ID: mdl-31660615

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.


Cochlear Implants , Vestibular Evoked Myogenic Potentials , Acoustic Impedance Tests , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Saccule and Utricle/physiology , Young Adult
10.
Med Princ Pract ; 28(1): 23-27, 2019.
Article En | MEDLINE | ID: mdl-30326473

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.


Biomarkers/blood , Blood Platelets , Hearing Loss, Sensorineural/blood , Hearing Loss, Sudden/blood , Lymphocytes , Neutrophils , Adult , Aged , China , Female , Humans , Lymphocyte Count , Male , Middle Aged , Platelet Count , Prognosis , Young Adult
11.
Article En | MEDLINE | ID: mdl-29672320

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.


Auditory Threshold/physiology , Cochlear Implantation/methods , Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Loss, Sensorineural/surgery , Labyrinth Diseases/physiopathology , Child , Child, Preschool , Cochlear Implants , Female , Hearing/physiology , Hearing Loss, Sensorineural/physiopathology , Hearing Tests , Humans , Labyrinth Diseases/surgery , Male , Postoperative Period , Treatment Outcome
12.
Cell Mol Biol Lett ; 23: 6, 2018.
Article En | MEDLINE | ID: mdl-29483928

BACKGROUND: Laryngeal cancer tends to have a very poor prognosis due to the unsatisfactory efficacy of chemotherapy for this cancer. Multidrug resistance (MDR) is the main cause of chemotherapy failure. The proto-oncogene c-fos has been shown to be involved in the development of MDR in several tumor types, but few studies have evaluated the relationship between c-fos and MDR in laryngeal cancer. We investigated the role of c-fos in MDR development in laryngeal cancer cells (cell line: human epithelial type 2, HEp-2) using the chemotherapeutic vincristine (VCR). METHODS: HEp-2/VCR drug resistance was established by selection against an increasing drug concentration gradient. The expressions of c-fos and multidrug resistance 1 (mdr1) were measured using qPCR and western blot. C-fos overexpression or knockdown was performed in various cells. The intracellular rhodamine-123 (Rh-123) accumulation assay was used to detect the transport capacity of P-glycoprotein (P-gp, which is encoded by the mdr1 gene). RESULTS: HEp-2 cells with VCR-induced resistance (HEp-2/VCR cells) were not only resistant to VCR but also evolved cross-resistance to other chemotherapeutic drugs. The expressions of the c-fos and mdr1genes were significantly higher in the HEp-2/VCR cells than in control cells. C-fos overexpression in HEp-2 cells (c-fos WT) resulted in increased P-gp expression and increased the IC50 for 5-FU. C-fos knockdown in the HEp-2/VCR cells (c-fos shRNA) resulted in decreased P-gp expression and decreased IC50 for 5-FU. An intracellular Rh-123 accumulation assay showed that the mean intracellular fluorescence intensity (MFI) was lower in the HEp-2/VCR cells than in HEp-2 cells. C-fos WT cells also showed lower MFI. By contrast, c-fos shRNA cells exhibited a higher MFI than the control group. CONCLUSION: C-fos increased the expression of P-gp and mdr1 in the HEp-2/VCR cells, and enhanced the efflux function of the cells, thereby contributing to the development of MDR.


Drug Resistance, Neoplasm , Laryngeal Neoplasms/metabolism , Proto-Oncogene Proteins c-fos/metabolism , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm/genetics , Gene Knockdown Techniques , Humans , Laryngeal Neoplasms/genetics , Proto-Oncogene Mas , Proto-Oncogene Proteins c-fos/genetics , Up-Regulation , Vincristine/pharmacology
13.
Int J Pediatr Otorhinolaryngol ; 102: 1-6, 2017 Nov.
Article En | MEDLINE | ID: mdl-29106852

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.


Acoustic Impedance Tests/methods , Cochlear Implantation/methods , Cochlear Implants/adverse effects , Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Loss, Sensorineural/surgery , Telemetry/methods , Adolescent , Auditory Threshold/physiology , Child , Child, Preschool , Cochlea/abnormalities , Female , Hearing Loss, Sensorineural/physiopathology , Humans , Male , Postoperative Care , Postoperative Period
14.
Anal Biochem ; 433(2): 86-91, 2013 Feb 15.
Article En | MEDLINE | ID: mdl-23103400

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.


Antigens/metabolism , Epithelial Cells/metabolism , Gene Knockdown Techniques , Nasal Mucosa/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Adult , Antigen Presentation/genetics , Antigens/genetics , Biological Transport/genetics , Cell Line , Endosomes/genetics , Endosomes/metabolism , Epithelial Cells/pathology , Humans , Lysosomes/genetics , Lysosomes/metabolism , Male , Nasal Mucosa/pathology , Rhinitis, Allergic , Rhinitis, Allergic, Perennial/genetics , Rhinitis, Allergic, Perennial/metabolism , Rhinitis, Allergic, Perennial/pathology , Ubiquitin/genetics , Ubiquitin-Protein Ligases/genetics
15.
Cell Mol Immunol ; 10(1): 78-83, 2013 Jan.
Article En | MEDLINE | ID: mdl-22941409

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.


Enterotoxins/immunology , Food Hypersensitivity/immunology , Haptens/immunology , Peptides/immunology , Th2 Cells/immunology , Animals , Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Dendritic Cells/immunology , Dendritic Cells/pathology , Female , Food Hypersensitivity/etiology , Food Hypersensitivity/pathology , Humans , Intestines/immunology , Intestines/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Rhinitis, Allergic, Perennial/etiology , Rhinitis, Allergic, Perennial/immunology , Rhinitis, Allergic, Perennial/pathology , Sinusitis/etiology , Sinusitis/immunology , Sinusitis/pathology , Th2 Cells/pathology
16.
J Biol Chem ; 287(42): 35318-35323, 2012 Oct 12.
Article En | MEDLINE | ID: mdl-22936803

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.


Bacterial Proteins/metabolism , Bacterial Toxins/metabolism , DNA-Binding Proteins/metabolism , Enterotoxins/metabolism , Epithelial Cells/enzymology , Intracellular Signaling Peptides and Proteins/metabolism , Nasal Mucosa/enzymology , Nuclear Proteins/metabolism , Proteolysis , Staphylococcus aureus/metabolism , Ubiquitin-Protein Ligases/metabolism , Adult , Bacterial Proteins/genetics , Bacterial Toxins/genetics , Cell Line , DNA-Binding Proteins/genetics , Endosomes/genetics , Endosomes/metabolism , Epithelial Cells/microbiology , Female , Humans , Intracellular Signaling Peptides and Proteins/genetics , Lysosomes/genetics , Lysosomes/metabolism , Male , Nasal Mucosa/microbiology , Nuclear Proteins/genetics , Tumor Necrosis Factor alpha-Induced Protein 3 , Ubiquitin-Protein Ligases/genetics
17.
Article Zh | MEDLINE | ID: mdl-22870723

OBJECTIVE: To investigate the new method of modified skin flap of external canal in auditory canal shaping to enlarge at radical mastoidectomy in endaural incision. METHOD: From 1999 to 2009, 412 patients with 428 ears in operation were randomly divided into two groups. Patients underwent open mastoidectomy and some patients were performed concurrent tympanoplasty. A group (control group)were operated in traditional skin flap of external canal, B group is modified group. Bleed and effusion from the wound surface, the time of dry ear and the change of diameter of extermal acoustic meatus after one year were observed after the surgeries and deal the results with SPSS. RESULT: The difference had statistical significance in bleed and effusion from the wound surface, the time of dry ear and the shrink of external acoustic meatus in 12 months among two groups. CONCLUSION: Modified skin flap of external canal in auditory canal shaping to enlarge can help to make a no-wound dehiscence by wiping out the raw surface of external acoustic meatus. It is better than traditional skin flap of external canal.


Ear Canal/surgery , Mastoid/surgery , Surgical Flaps/transplantation , Tympanoplasty/methods , Aged , Humans , Postoperative Complications , Semicircular Canals
18.
J Leukoc Biol ; 90(4): 751-9, 2011 Oct.
Article En | MEDLINE | ID: mdl-21724807

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.


Antigens, Neoplasm/immunology , Epithelial Cells/immunology , Immune Tolerance/immunology , Integrins/immunology , Intestinal Mucosa/immunology , T-Lymphocytes, Regulatory/immunology , Th2 Cells/immunology , Animals , Antigens/immunology , Cell Line , Dendritic Cells/cytology , Dendritic Cells/immunology , Epithelial Cells/cytology , Exosomes/immunology , Intestinal Mucosa/cytology , Mice , Mice, Inbred BALB C , T-Lymphocytes, Regulatory/cytology , Th2 Cells/cytology , Transforming Growth Factor beta/immunology
19.
Gastroenterology ; 141(1): 249-58, 258.e1-2, 2011 Jul.
Article En | MEDLINE | ID: mdl-21569774

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.


CD3 Complex/immunology , Cytokines/immunology , Enteritis/immunology , Immune Tolerance , Immunity, Mucosal , Intestines/immunology , Mouth Mucosa/immunology , Th2 Cells/immunology , Animals , Apoptosis , Blotting, Western , Cells, Cultured , Dendritic Cells/immunology , Disease Models, Animal , Enteritis/genetics , Enteritis/pathology , Enteritis/prevention & control , Flow Cytometry , Genes, T-Cell Receptor , Immunohistochemistry , Intestines/pathology , Mice , Mice, Inbred BALB C , Mice, Transgenic , Ovalbumin , Phagocytosis , Receptors, Cytokine/immunology , Th2 Cells/pathology , Th2 Cells/transplantation
20.
Am J Med Sci ; 341(1): 40-7, 2011 Jan.
Article En | MEDLINE | ID: mdl-20924287

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.


Cytokines/metabolism , Nasal Polyps/etiology , Nasal Polyps/pathology , Adult , Cytokines/genetics , Female , Gene Expression Regulation/physiology , Humans , Male , Middle Aged , Nasal Mucosa/metabolism , Nasal Mucosa/pathology , Nasal Polyps/surgery , OX40 Ligand/genetics , OX40 Ligand/metabolism , Receptors, Cytokine/genetics , Receptors, Cytokine/metabolism , Receptors, Tumor Necrosis Factor/genetics , Receptors, Tumor Necrosis Factor/metabolism , Thymic Stromal Lymphopoietin
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