Table of Content

27 July 2023 Volume 37 Issue 4

  

Classification, pathogenesis, and treatment advances of chronic subjective tinnitus

CHEN Zhuoyi, ZHENG Yiqing, YANG Haidi

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  1-12.  doi:10.6040/j.issn.1673-3770.0.2023.137

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Chronic subjective tinnitus characterized by a high incidence rate, diverse clinical manifestations, and a complex pathological mechanism, is a common symptom in otolaryngology. Tinnitus classification and research on its neurophysiological mechanisms serve as a basis for guiding clinical diagnosis and individualized precision medical treatment. In recent years, an increasing number of tinnitus studies have introduced novel concepts in these domains. Emerging evidence shows that dimensional variability of tinnitus characteristics may provide a more accurate understanding of the heterogeneous nature of tinnitus compared to traditional subtype classification, thereby holding significant potential for clinical research and diagnosis applications. In addition, a newly developed tinnitus network model, integrates the neurophysiological mechanisms of tinnitus and its associated complications, further advancing the theoretical basis for individualized tinnitus treatment. This article provides a summary of the dimensional network model for tinnitus classification and the triple network model of tinnitus-associated complications. Additionally, it briefly outlines the common treatment methods for tinnitus incorporating updated guidelines and the latest evidence-based medicine, providing a valuable reference for readers.

Progress in acoustic therapy for chronic subjective tinnitus

LUO Yiwen, XIAO Yongtao, GAO Minqian, YANG Jiayi, YANG Haidi

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  13-23.  doi:10.6040/j.issn.1673-3770.0.2023.108

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Chronic subjective tinnitus is a high-incidence disease, and can seriously effect patients' mood, sleep, and quality of life. Recently, the development of cortical function detection technology has considerably promoted research investigating the mechanisms underlying chronic subjective tinnitus. Evidence supports sound therapy as beneficial for tinnitus. However, its efficacy and applicability remain controversial. In the present study, we summarized the mechanisms of chronic subjective tinnitus and reviewed the current research progress investigating the treatment of this disease both domestically and abroad. We expect our results to serve as a reference to aid further research and the clinical applications of sound therapy.

The role and mechanism of abnormal central nervous system activity in the occurrence of tinnitus

ZHANG Hong, LI Xin

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  24-29.  doi:10.6040/j.issn.1673-3770.0.2023.142

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Tinnitus refers to the perception of noise without an external sound source, ear or intracranial buzzing, hoarseness, and other abnormal sound illusion phenomena. With the development of clinical research on the pathogenesis of tinnitus, additional studies and analyses show that central nervous system activity is closely related to the pathogenesis of tinnitus. However, the factors affecting central nervous system activity are complex and diverse. Therefore, it is critical to investigate tinnitus symptoms through the mechanism of the central nervous system to relieve the clinical symptoms and the effects of tinnitus on daily work and life. Thus, this study observed that the pathogenesis of subjective tinnitus is closely related to the central nervous system. Limbic system function may also contribute to the development of tinnitus by blocking the pathways of these mechanisms; it may also contribute to the relief of tinnitus symptoms, thus providing a new approach to treating tinnitus patients.

A randomized controlled clinical trial of sound therapy combined with medication in the treatment of chronic subjective tinnitus

DONG Hongsong, WANG Chunli, YU Yanping, CHEN Tao, NIE Guohui

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  30-37.  doi:10.6040/j.issn.1673-3770.0.2023.210

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Objective To investigate the short-term efficacy and difference between sound therapy combined with medication and medication alone in patients with chronic subjective tinnitus. Methods A total of 64 patients with chronic tinnitus(> 6 months)were included in the study. Using a randomized controlled method, patients were divided into two groups(n=32 each): combined sound and drug(combined treatment); and drug alone. Based on tinnitus counseling, the drug group was administered oral ginkgo biloba extract tablet, while the combined group was administered personalized multiple compound sound therapy based on drug therapy. The Tinnitus Handicap Inventory(THI), visual analog scale(VAS), and Self-rating Anxiety Scale(SAS)scores were compared between the two groups before and after 1 month of treatment. The effectiveness rate of tinnitus treatment was compared between the two groups and possible factors affecting treatment efficacy were analyzed. Results THI, VAS, and SAS scores in the drug and combined groups were decreased after treatment(P<0.05). Differences in THI and VAS scores in the combination treatment group were greater than those in the drug group before and after treatment(P<0.05). There was no statistical difference in SAS score between the two groups before and after short-term treatment. The total treatment effectiveness rate in the combined treatment group was higher than that of the drug group(P<0.05). Sex, age, tinnitus frequency, tinnitus side, tinnitus tone, and hearing loss frequency band were not significantly correlated with tinnitus treatment efficacy(P>0.05). Conclusion Based on tinnitus consultation, both sound therapy combined with medication and drug alone have certain efficacy in the treatment of tinnitus. Compared with drug alone, however, combined treatment more effectively alleviated subjective severity of the impact of tinnitus on patient life, and yielded a higher total effectiveness rate. Sex, age, tinnitus frequency, tinnitus side, tinnitus tone, and hearing loss frequency band matching and other factors did not exert significant influence on the efficacy of tinnitus treatment.

Efficacy of compound sound therapy for patients with tinnitus and sudden deafness

XU Haiyan, CAO Wei, FAN Dachuan

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  38-45.  doi:10.6040/j.issn.1673-3770.0.2022.161

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Objective The objectives of this study were to evaluate the efficacy of compound sound therapy and provide guidance for clinical practice for patients with tinnitus and sudden deafness. Methods We retrospectively analyzed clinical data from 112 patients with tinnitus and unilateral sudden deafness who were treated in our department between January 2017 and August 2020. Patients were randomly divided into two groups according to the treatment: 54 patients in the control group were treated with medical therapy, and 58 patients in the observation group were treated with medical therapy in addition to compound sound therapy. Clinical data were collected for age, sex, laterality, and duration. All patients received the pure-tone audiometry and tinnitus tests, including loudness and residual inhibition. The Tinnitus Handicap Inventory, Visual Analogue Scale and Self-Rating Anxiety Scale scores were measured pre-and post-therapy. The compound sounds were remixed with noise/pure tone, natural sound, and music clips. The masking frequency of background sound was consistent with the tinnitus frequency of patients, and the main frequency of music clips covered the tinnitus frequency. Results The means of the pure tone hearing thresholds of the two groups after treatment were significantly lower at 2 weeks, 1 month, and 3 months after treatment. The total effective rates of hearing in the control group were 53.7%, 77.8%, and 80.3%, and the rates in the observation group were 55.2%、75.9%、and 77.6% at 2 weeks, 1 month, and 3 months, respectively. No significant difference was found between the two groups(P>0.05). The THI, VAS, and SAS scores significantly decreased after treatment in both groups, The total effective rates of tinnitus in the observation group were 62.1% and 81.1%, which were significantly better than those in the control group, which were 53.7% and 59.3% at 1 month and 3 months after treatment, respectively. The highest effect was observed in the observation group at 3 months after the compound sound therapy. This effect was better than at 1 month post-treatment, and the difference was statistically significant(all P<0.05). Conclusion Patients with tinnitus and sudden deafness showed adaptations with compound sound therapy and acquired more benefits from extension of treatment duration.

Correlation between the anxiety-depression state and idiopathic tinnitus prognosis

WU Bo, HUANG Tiande, YAN Bin, CHEN Yi, TANG Yong

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  46-52.  doi:10.6040/j.issn.1673-3770.0.2022.551

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Objective To study the anxiety and depression status of patients with idiopathic tinnitus and analyze the factors that may affect the prognosis of tinnitus. Methods The clinical data of 100 patients with idiopathic tinnitus were retrospectively analyzed. A uniform tinnitus treatment protocol was used. Patients were followed -up after 12 weeks of treatment to evaluate the efficacy and analyze the factors that may affect the prognosis of tinnitus. Results The effect of each scale after treatment was more than 0.50, and the difference was statistically significant(P<0.05). The GAD-7 score(Z=-6.482, P<0.001)and PHQ-9 score(Z=-6.070, P<0.001)were higher in the moderate-severe than in the mild tinnitus group. There were no statistically significant differences in the prognosis of tinnitus between the groups in terms of sex, age, side of tinnitus, loudness of tinnitus, frequency of tinnitus, degree of hearing loss, and duration of tinnitus disease(P>0.05). The pre-treatment THI score(OR=1.028, P=0.003), post-treatment improvement in anxiety(OR=5.637, P<0.001), post-treatment improvement in depression(OR=4.200, P=0.001), sleep improvement after treatment(OR=4.744, P=0.008)and clinical cure of tinnitus(OR=7.306, P<0.001)were independently associated with tinnitus prognosis. The multiple linear regression analysis results suggested that the pre-treatment THI score, clinical cure of tinnitus, and anxiety improvement after treatment positively correlated with tinnitus prognosis(all P<0.05). Conclusion Gender, age, side of tinnitus, loudness of tinnitus, frequency of tinnitus, degree of hearing loss, and tinnitus duration were not significantly associated with the prognosis. Conversely, the pre-treatment THI score, anxiety improvement after treatment, depression improvement after treatment, sleep improvement after treatment, and clinical cure of tinnitus were independently associated with tinnitus prognosis. The overall severity of tinnitus was positively associated with the anxiety-depression status. The anxiety-depression status of patients in the moderate-severe tinnitus group was more severe than that in the mild tinnitus group. Hence, clinical attention should be paid to the psychosocial status of patients with moderate-severe tinnitus.

Clinical observation of “Six acupoints for treating tinnitus”in the treatment of patients with spleen and stomach deficiency and study of brain effect mechanism

LIU Guangyu, TAN Junying, HUO Yan, ZHANG Jianning, LI Ming

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  53-61.  doi:10.6040/j.issn.1673-3770.0.2023.099

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Objective We first observe the clinical effect of “Six acupoints for treating tinnitus” in the treatment of tinnitus patients with spleen and stomach deficiency, and then adopt a longitudinal study on the treatment of tinnitus with acupuncture by using fMRI which investigates their brain effect mechanism. Methods We select 65 tinnitus patients that were diagnosed with chronic, moderate to severe tinnitus(THI≥38 points)and have spleen and stomach deficiency according to TCM syndrome differentiation. These patients were admitted to the Department of Otorhinolaryngology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese medicine from August 2020 to January 2022. In addition, patients were randomized into an observation group(the “Six acupoints for treating tinnitus” treatment group)and a control group(the basic treatment group). The former group was receiving communication puzzle-solving and acoustic therapy. The latter group was treated with acupuncture at “Six acupoints for treating tinnitus”(twice a week, for five weeks)in addition to the basic treatment. After treatment and follow-up period(two-time points: 1 month and 3 months after the treatment), we employ THI and PSQI to assess the improvement of clinical symptoms in these two groups. Finally, we make a comparison study by adopting ALFF, ReHo, and FC as data analysis methods to compare the changes in brain functional activities before and after acupuncture at “Six acupoints for treating tinnitus” in tinnitus patients with spleen and stomach deficiency. Results Compared with control group, the scores of THI and PSQI in patients with chronic tinnitus in observation group were significantly reduced(P<0.05). Compared with those before treatment, the scores of THI and PSQI in both groups were significantly decreased after treatment(P<0.05). The total effective rates at the end of treatment, 4 weeks, and 12 weeks after treatment in observation group were 90.63%, 87.50%, and 87.50%, respectively. Nevertheless, those in control group were 75.76%, 72.73%, and 66.67%, respectively. To put it differently, the clinical efficacy in observation group was more significant than that in control group. The ALFF values in the right putamen nucleus and right insula, and the ReHo values of the right fusiform gyrus and the right lingual gyrus were decreasing after acupuncture treatment of tinnitus patients in the observation group. Functional connectivity analysis showed that the functional connectivity between the right putamen nucleus and the right frontal gyrus, the right angular gyrus, and the left paracentral lobular decreased after treatment when the right putamen nucleus was set as the seed point. Similarly, the functional connection strength between the right lingual gyrus and the left medial superior frontal gyrus or left superior frontal gyrus decreased after treatment when the right lingual gyrus was used as the seed point. In observation group, the change of ALFF value in the right putamen nucleus was positively correlated with PSQI score(P<0.001). Conclusion “Six acupoints for treating tinnitus” acupuncture treatment has a more significant effect on improving the severity of tinnitus patients, reducing tinnitus loudness, and relieving concomitant symptoms. The decrease in the functional connection between the putamen nucleus, the lingual gyrus, and the prefrontal cortex after acupuncture treatment may be the important central regulation mechanism of “Six acupoints for treating tinnitus” acupuncture in the treatment of tinnitus patients with spleen and stomach deficiency.

Analysis of Cochlear function in young and middle-aged tinnitus patients with normal pure tone audiometry threshold

XIONG Binbin, LU Ziang, YANG Jing, XU Wenqiang, ZHOU Luru, SUN Pinyuan, YUAN Ding, ZHU Jiahao

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  62-67.  doi:10.6040/j.issn.1673-3770.0.2023.093

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Objective Otoacoustic emission(OAE)data were analyzed to explore cochlear function in young and middle-age adults with tinnitus and normal pure-tone thresholds. Methods Data from 30 non-tinnitus patients with normal pure-tone average(PTA)threshold and 64 young and middle-age patients with tinnitus were collected from a tinnitus clinic from September 2021 to June 2022. All patients underwent objective testing by audiologists including distortion product otoacoustic emission(DPOAE), transient evoked otoacoustic emission(TEOAE), and spontaneous otoacoustic emission(SOAE). Results were compared, and the frequency of SOAE and the frequency of precision tinnitus matching were analyzed and compared. Results There were no statistically significant differences in sex, age, or average PTA threshold between the tinnitus patients and normal young individuals(P1=0.079,P2=0.078,P3=0.0810, respectively). DPOAE testing revealed no statistically significant differences in pass rates for all frequencies between the tinnitus and the control groups(P>0.05)except at 6000 Hz(P<0.05). In contrast, TEOAE testing revealed a statistically significant difference in pass rate for all frequencies between the two groups(P<0.05). Elicited SOAE rates in the control and tinnitus groups were 31.67% and 43.62%, respectively, ranging from 1 211 Hz to 4 453 Hz and 859 Hz to 4 570 Hz, respectively, with no statistical difference between the groups(χ2=2.199, P=0.138). Finally, there was no significant correlation between the frequency of SOAE and the frequency of precision tinnitus matching(r=0.1143, P=0.540). Conclusion DPOAE and TEOAE pass rates in young and middle-age patients with tinnitus and normal PTA threshold were significantly different from individuals without tinnitus. The differences occurred at some frequency points, which suggests early stages of mild cochlear damage but not yet affecting the threshold. As a “hidden” injury among patients with tinnitus, this warrants attention.

Factors influencing the development of facial paralysis and the associated prognosis in patients with herpes zoster virus infection

FAN Tao, ZHU Mengdie, XIE Donghai, LI Xiangsheng, SONG Guilin, XIAO Xuping

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  68-74.  doi:10.6040/j.issn.1673-3770.0.2022.216

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Objective The aim of this study was to analyze the influencing factors and predictors of adult facial herpes zoster virus infection complicated with facial paralysis, and to explore the risk factors affecting the prognosis of facial paralysis. Methods From January 2016 to April 2022, 125 patients with herpes zoster virus infections of the ear, who were admitted to the Otolaryngology Department of Changsha Affiliated Hospital of Hunan Normal University and Ningxiang Hospital of Traditional Chinese Medicine Hospital were retrospectively analyzed. Clinical data, routine blood parameters, and high-sensitivity C-reactive protein(hs-CRP)concentrations were compared between the facial paralysis and non-facial-paralysis groups. The predictive value of the receiver operating characteristic curve evaluation index for herpes zoster complicated with facial paralysis was determined. Based on the occurrence of facial paralysis sequelae, the patients were then divided into the sequelae and non-sequelae groups, and independent risk factors affecting their prognosis were analyzed. Results The hs-CRP concentration and lymphocyte-to-monocyte ratio(LMR)were independent influencing factors and had predictive value for herpes zoster virus infection complicated with facial paralysis. When the cut-off value of hs-CRP concentration was less than or equal to 3.05 mg/dL, the sensitivity was 50.77%, the specificity was 86.67%, the positive predictive rate was 80.49%, and the negative predictive rate was 61.9%. When the cut-off LMR value was greater than or equal to 2.89, the sensitivity was 44.44%, the specificity was 88.64%, the positive predictive rate was 87.8%, and the negative predictive rate was 46.43%. An age greater than 50 years, an initial degree of facial paralysis greater than grade III, more than 72 hours from facial paralysis to hormone therapy, and no antiviral treatment before facial paralysis were independent risk factors for facial paralysis sequelae in patients with herpes zoster virus infections. Conclusion hs-CRP concentration and LMR have a certain reference value in predicting whether herpes zoster virus infections of the ear will be complicated with facial paralysis. The use of antiviral drugs before the onset of facial paralysis may reduce the irreversible sequelae.

Meta-analysis of randomized controlled trials of acupoint application in treatment of children with allergic rhinitis

BI Xiaoyun, MA Benxu, WANG Xinru, LI Xuhao, YANG Jiguo

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  75-85.  doi:10.6040/j.issn.1673-3770.0.2022.189

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Objective To evaluate the efficacy of acupoint application in the treatment of children with allergic rhinitis(AR)by meta-analysis. Methods PubMed, the Cochrane Library, CNKI, VIP, WanFang, and CBM, were searched comprehensively for randomized controlled trials(RCT)of acupoint application used in treatment of children with allergic rhinitis, with retrieval time set from establishment of each database to April 17, 2022. RevMan 5.3 and Stata 14.0 were used to analyze relevant outcome indicators. Results A total of 19 RCTs were included, with a total sample size of 1669 cases. Meta-analysis results showed that the effective rate of acupoint application combined with traditional Chinese medicine in the treatment of children with allergic rhinitis was significantly better than the control group of traditional Chinese medicine alone(RR=1.12, 95%CI ［1.03,1.21］, P=0.006). The effective rate of acupoint application combined with Western medicine in the treatment of children with allergic rhinitis was significantly better than Western medicine alone(RR=1.28, 95%CI ［1.14,1.44］, P<0.001). The clinical effect of acupoint application alone was significantly better than Western medicine alone(RR=1.23, 95%CI ［1.15,1.31］, P<0.001). The clinical effect of simple acupoint application is equivalent to that of simple application of traditional Chinese medicine(RR=1.45, 95%CI ［0.84,2.49］, P=0.18). Acupoint application and Western medicine can both reduce Eosinophil and Immunoglobulin E levels, but there were no differences in reduction effects. Acupoint application can significantly reduce Interleukin-4 levels, enhance Interferon-γ levels, and improve clinical symptoms. Conclusion Acupoint application therapy is effective, safe, and reliable for clinical treatment of children with allergic rhinitis, and can be widely used.

Prescription regularity analysis in treating olfactory dysfunction from ancient Chinese medicine literature

ZHU Jinxiang, ZHOU Min, WANG Ruizhi, LI Dan, FANG Caishan, CHEN Tengyu, LIN Manqing, RUAN Yan

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  86-95.  doi:10.6040/j.issn.1673-3770.0.2022.203

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Objective Data mining method was used to analyze the prescription regularity of olfactory dysfunction recorded in ancient Chinese medicine literature. We aimed to provide a prescription reference for the way for treating olfactory dysfunction. Methods Traditional Chinese medicine(TCM)prescriptions from the Zhong Yi Dian Hai software for the treatment of olfactory dysfunction were retrieved, and the Excel 2016 software was utilized to form an olfactory dysfunction prescription database by importing the original data. Data were imported into the ancient and modern medical case cloud platform for prescription frequency, TCM frequency, TCM attributes, and TCM cluster, correlation, and complex network analyses. Results A total of 115 clearly recorded prescriptions were obtained, among which Xinyi San had the highest recorded frequency. In the TCM frequency statistics, the top 13 herbs included Asarum, Saposhnikovia divaricata, Ligusticum wallichii, Rattletop, Akebia quinata, Muskmelon pedicel, Radix angelicae dahuricae, Notopterygium root, liquorice, Prepared radix glycyrrhizae, Astragalus membranaceus, Ephedra, and Ginseng. It was found that warm, mild warm, and cold were the main characteristics among the four natures of herbs. Spicy, sweet, and bitter are the most common flavors among the five flavors of herbs. Lung and spleen meridians were the predominant meridians. According to data statistics, the most common uses for TCM include the following: dispelling wind and relieving pain, warming lungto reduce watery phlegm, dispelling wind and dispersing cold, and relieving stuffy nose. Three groups of TCM were obtained by conducting a cluster analysis of the top 10 TCM(I: Asarum and Muskmelon pedicel; II: Akebia quinata, Ligusticum wallichii, and Prepared radix glycyrrhizae; III: Rattletop, Saposhnikovia divaricate, Notopterygium root, Radix angelicae dahuricae, and liquorice). Correlation analysis was conducted by adjusting the confidence and support degrees to select 13 groups with the most relevant TCM compatibility, among which Rattletop, Saposhnikovia divaricata, Ligusticum wallichii, and Asarum were the most compatible. Based on the complex network analysis, nine core TCMs were obtained(Ligusticum wallichii, Asarum, Rattletop, Saposhnikovia divaricata, Akebia quinata, Radix angelicae dahuricae, Notopterygium root, Muskmelon pedicel, and liquorice), which functions in dispersing external evil and promoting clearance of nasal passages, the composition of which is similar to Xinyi San. Conclusion The ancient TCM treatments used for olfactory dysfunction are drugs for the diaphoretic drug, which is represented by the lung meridian of hand-taiyin and the spleen meridian of foot-taiyin. Moreover, attention should be paid to the etiology and pathogenesis of the disease and it should be determined whether the olfactory dysfunction was caused by the deficiency of Qi-Xue-Yin-Yang and qi deficiency so that treatment can be administered accordingly.

Role of CD4⁺ T cells from nasal mucosa in the pathogenesis of patients with seasonal allergic rhinitis

HOU Lingxiao, ZHANG Changcui, XU Anting, FAN Xintai, WANG Na

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  96-104.  doi:10.6040/j.issn.1673-3770.0.2023.130

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Objective To explore the key biological mechanisms of CD4⁺ T cells involved in the pathogenesis of seasonal allergic rhinitis(SAR). Methods Gene expression data were obtained from the GSE49782 dataset in the Gene Expression Omnibus. GEO2R was used to screen the genes differentially expressed between CD4⁺ T cells isolated and extracted from nasal mucosa biopsy tissues of SAR patients before and after stimulation by a birch pollen extract. Metascape was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses. The STRING dataset was used to analyze the protein-protein interactions of differentially expressed genes(DEGs). X2K was used to explore the regulatory relationship between DEGs and their transcription factors. Results A total of 74 DEGs were screened based on an adjusted P-value of <0.05 and | logFC |>0.585. Of these DEGs, 8 were upregulated and 66 were downregulated. GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in proteins and pathways related to the intercellular junction and actin filament assembly. Through transcription factor analysis of DEGs and further analysis of the protein-protein interaction networks, five hubs of DEGs(ASL, CTTN, EPS8, FNBP1L, and SH3KBP1)as well as key transcription factors and important kinases(SIN3A, CDK1, and GSK3B)were found to play important roles in the pathogenesis of SAR. Conclusion CD4⁺ T cells in the nasal mucosa may affect the pathogenesis of SAR through a series of biological processes, for example, by regulating intercellular connections through their key expressed genes. The ASL, CTTN, EPS8, FNBP1L, and SH3KBP1 hubs of DEGs as well as key transcription factors and important kinases, such as SIN3A, CDK1, and GSK3B, could be involved in the occurrence and development of SAR. These novel findings will further our understanding of the molecular biological mechanism of SAR occurrence and development and will help in exploring effective therapeutic options.

Misdiagnosis of primary nasopharyngeal tuberculosis: a case report and literature review

LI Guangjin, WANG Yan, LIU Feifei, SONG Xicheng, SUN Yan

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  105-110.  doi:10.6040/j.issn.1673-3770.0.2022.530

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Objective This study aimed to provide a clinical reference for otolaryngologists by identifying the clinical characteristics of nasopharyngeal tuberculosis and causes of misdiagnosis. Methods This retrospective analysis included data of one case of misdiagnosis of primary nasopharyngeal tuberculosis(PNT). We analyzed the clinical characteristics of the case and reasons why it was easily misdiagnosed, considering the relevant literature. Results The clinical manifestations of PNT were related to the degree of hyperplasia of the nasopharyngeal lesions, which usually do not have clinical tuberculosis-related manifestations and cannot easily be distinguished from chronic nasopharyngitis. In cases wherein tuberculosis diagnosis is not clear enough based on pathological examination, tuberculosis-related tests should be performed and patients should be instructed to adhere to close follow-up. Regarding treatment, systemic anti-tuberculosis agents are still the mainstay of therapy. Conclusion PNT is relatively rare and lacks typical clinical manifestations, making it be easily misdiagnosed. Histopathology combined with tuberculosis-related tests could help improve diagnosis of PNT. Furthermore, regularly close follow-up is also an important key factor in avoiding misdiagnosis.

Net Meta-analysis and data mining of patients with acute pharyngitis managed with Chinese medicine

LI Zepeng, LI Wenjian, SUN Zhijia

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  111-118.  doi:10.6040/j.issn.1673-3770.0.2022.173

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Objective This study aimed to explore the use of Chines- patent medicines in managing patients with acute pharyngitis, and to compare their efficacy against commonly used drugs. Methods Clinical studies of Chinese-patent medicines for acute pharyngitis, published until April 20, 2022, were collected from PubMed, Embase, Cochrane Library, web of science, CNKI, Wanfang, Sinomed, and VIP. Meta-analysis and data mining were done with the Stata software and R software. Results A total of 202 clinical studies and 141 types of Chinese-patent medicines were collected. Of which, a watermelon cream preparation was the most frequently studied Chinese-patent medicine, followed by Shufengjiedu capsules. The main symptoms of exuberant lung-stomach heat included sore swollen throat, dry throat and thirst, and gum swelling and pain. On the other hand, the main symptoms of wind-heat assailing the outer body included pharyngeal redness and swelling, dry throat, hoarseness, hissing, and fever. A total of 33 randomized control trials, 14 interventions, and eight types of Chinese-patent medicines were included in our meta-analysis, which showed that Sufengjiedu capsules combined with antibiotics, watermelon cream preparation, Qingyan drops combined with antibiotics, Guaizijin, and Yinhuang preparations were more effective than single vse antibiotics. Moreover, our net meta-analysis revealed that the Yinhuang preparation(SUCRA=0.87), sufengjiedu capsule combined with antiviral drugs(SUCRA=0.85), and watermelon cream preparation(SUCRA=0.72)had the greatest efficiency rates. Conclusion At present, the most used clinical research on the treatment of acute pharyngitis with Chinese-patent medicine involves the use of watermelon cream preparation. The most common pattern is wind-heat assailing the outer body. Our metanalysis revealed that the efficacy of Chinese patent medicines was non-inferior to that of antibiotics alone. Of which, the Yinhuang preparation displayed the best efficacy.

Laryngeal adenoid cystic carcinoma: four cases and a literature review

WEN Feng, ZHANG Chi, HU Xihao, DONG Bingwan, QIN Yong, ZHAO Enmin

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  119-125.  doi:10.6040/j.issn.1673-3770.0.2022.171

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Objective To analyze the clinical characteristics of laryngeal adenoid cystic carcinoma. Methods We performed a retrospective study of 4 patients with laryngeal adenoid cystic carcinoma(LACC)treated in the Department of Otolaryngology, Head and Neck surgery of Peking University First Hospital from 2018-2021. The clinical manifestations, diagnosis, treatment, and prognosis were summarized and analyzed in combination with a literature review. Results The 4 patients comprised 3 women and 1 man. The most common symptoms were dyspnea(3 cases)and hoarseness(2 cases). The involved laryngeal subsites included the subglottis(2 cases)and the supraglottis(2 cases). Lung metastasis was suspected in 1 patient, while no distant metastases were observed in the rest. Total laryngectomy was performed in 2 patients, partial laryngectomy was performed in 1 patient, and palliative tumor resection combined with radiotherapy was performed in 1 patient. The range of follow-up time varied from 8-42 months(median 20.5 months). No local recurrence or distant metastasis were observed. Conclusion LACC is a rare malignancy with a female predilection. This neoplasm is characterized by slow growth kinetics, submucosal spread, and perineural invasion. The main symptoms are dyspnea and hoarseness, and the lesions most likely to occur in the subglottic and supraglottic areas. Diagnosis is based on pathology, for which the characteristic biomarker is CD117, while molecular genetic examination reveals MYB gene translocation. The mainstay treatment of LACC is radical surgery, of which total laryngectomy is the most commonly used surgical modality, which may be supplemented with postoperative radiotherapy. Surgical patients have a better prognosis than non-surgical patients. Distant metastases may occur late and require long-term follow-up.

Association between homocysteine concentration and the MTHFR C677T polymorphism and hypertension in patients with obstructive sleep apnea hypopnea syndrome

CHEN Shangli, QIN Tao, CHEN Xuan, CHEN Ruojin, TANG Zhi

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  126-133.  doi:10.6040/j.issn.1673-3770.0.2022.166

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Objective The aim of this study was to investigate the relationships between homocysteine(Hcy)concentration and the C677T gene polymorphism in its key metabolic enzyme, methylenetetrahydrofolate reductase(MTHFR), and hypertension in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). Methods Eighty-five patients with OSAHS, diagnosed by sleep monitoring, and 77 patients without OSAHS were included in this study. We determined MTHFR gene polymorphisms and serum Hcy, fasting blood glucose, and hemoglobin A1c concentrations in blood samples collected from all patients. Serum Hcy concentrations were compared between the TT, CT, and CC genotypes of the MTHFR C677T polymorphism. The Hcy concentration, MTHFR C677T genotype, and C/T allele frequency were compared between patients with OSAHS and hypertension, patients with OSAHS without hypertension, and the patients without OSAHS and hypertension. The factors associated with hypertension in OSAHS patients were evaluated using univariate and multiple Logistic regression analyses. Results The Hcy concentrations for the CC, CT, and TT genotypes were 10.11(9.15, 11.07)mol/L, 10.86(9.58, 11.10)mol/L and 15.81(11.43, 50.76)mol/L, respectively. Hcy concentrations were higher for the TT genotype than the CT(P=0.005)and CC(P<0.001)genotypes. The Hcy concentrations in patients with OSAHS and hypertension, patients with OSAHS without hypertension, and patients without OSAHS and hypertension were 11.21(10.08, 13.60)mol/L, 9.93(9.30, 11.42)mol/L and 10.32(9.33, 11.23)mol/L, respectively. Hcy concentrations were higher in patients with OSAHS and hypertension than in patients with OSAHS without hypertension(P=0.027)and patients without OSAHS and hypertension(P=0.039). After controlling for other confounding factors, hyperhomocysteinemia(HHcy)concentration was an independent risk factor for hypertension in patients with OSAHS(OR=4.160; 95%CI: 1.054, 16.418). There were no statistically significant differences in MTHFR C677T genotype or C/T allele frequency among the three groups. Conclusion The MTHFR C677T polymorphism affects serum Hcy concentrations, with the TT genotype showing higher concentrations than the CT and CC genotypes. HHcy concentration is an independent risk factor for hypertension in OSAHS patients, but neither the MTHFR C677T polymorphism nor the C/T allele frequency were associated with hypertension in OSAHS patients.

The relationship between bacterial gas production and necrotizing fasciitis of neck

LI Dajian, WANG Yan, SONG Xicheng

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  134-138.  doi:10.6040/j.issn.1673-3770.0.2022.191

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Objective To compare the imaging findings of necrotizing fasciitis of the neck and other cervical space infections, and explore the relationship between the gas production of the infected bacteria and necrotizing fasciitis of the neck. Methods A retrospective study was conducted on 52 cases of cervical fascia space infection in our department from May 2015 to February 2020, including 18 cases of necrotizing fasciitis and 34 cases of non-necrotizing fasciitis. 18 cases underwent incision, debridement and catheter drainage in the necrotizing fasciitis group. 26 cases underwent incision, debridement and catheter drainage, and 8 cases underwent ultrasound-guided puncture biopsy and catheter drainage in the non-necrotizing fasciitis group. All cases were confirmed by operation or pathological biopsy and took purulent secretions for bacterial culture and drug sensitivity test during or after operation. All cases were examined by neck CT or MRI before operation. The previous history of surgical incision or puncture and the rupture of cervical space infection were excluded. Results In 18 cases of necrotizing fasciitis, there were 15 cases had air accumulation in the fascial space(83.3%); In 34 cases of non necrotizing fasciitis, 2 cases had air accumulation in the fascial space(5.9%).There was significant difference between the two groups(χ2=32.084 2, P<0.01). Bacterial culture results were positive in 14(77.8%)patients with necrotizing fasciitis. There were 5 cases of mixed infection, 13 cases of Streptococcus, 4 cases of Klebsiella pneumoniae, 1 case of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, and 1 cases of Acinetobacter baumannii in the necrotizing fasciitis group. In the non necrotizing fasciitis group, 12(35.3%)patients had positive bacterial culture results, and there were 4 Streptococcus, 2 Klebsiella pneumoniae, 1 Staphylococcus aureus, 1 coagulase negative staphylococcus, 1 Haemophilus influenzae, 1 Escherichia coli, 1 Enterobacter cloacae and 1 Acinetobacter baumannii in the non necrotizing fasciitis group. There was significant difference in the positive rate of bacterial culture between the two groups(χ2=8.496 7, P<0.01). Except one death in necrotizing fasciitis group, all other patients were cured. There was no recurrence after follow-up for 3-6 months. Conclusion The air accumulation in necrotizing fasciitis of neck is more than that in other infectious diseases of neck space.It is suggested that the gas production of bacteria may be closely related to the pathogenesis and development of necrotizing fasciitis of the neck. Early measures to block the generation and dissemination of gas may be of great significance for treatment.

Long-term progress of visual field defect for open-angle glaucoma patients with ab interno trabeculotomy with the trabectome

MENG Sukun, ZHANG Chun

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  139-148.  doi:10.6040/j.issn.1673-3770.0.2022.181

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Objective To observe the long-term efficacy of ab interno trabeculotomy with the Trabectome and the progress of visual field defect for open-angle glaucoma patients. Methods In this retrospective cohort study, 62 primary open-angle glaucoma patients who underwent ab interno trabeculotomy with the Trabectome were included. The main outcome measure was visual field, and the secondary outcome measures included intraocular pressure, the amount of glaucoma medications, and surgical complications. The Wilcoxon test was used to compare the postoperative intraocular pressure and the number of glaucoma medications with baselines. The Enhanced Glaucoma Staging System(GSS 2)was used to evaluate the severity of preoperative visual field defects and to stage the preoperative visual field. The parameters of diffuse visual field defect(mean defect of Octopus visual field test and mean deviation of Humphrey visual field test)in all follow-ups were analyzed by linear regression with time. Whether the visual field defect progressed or not was judged according to the slope of regression equation. Moreover, the risk factors of visual field defect progression were further explored. Results The preoperative intraocular pressure of all 62 cases was(20.9±7.5)mmHg and the preoperative number of glaucoma medications before was(2.6±1.2)species. After operation, intraocular pressure decreased to(17.6±3.4)mmHg(P=0.018)and the number of glaucoma medications decreased to(2.3±1.1)species(P=0.317)at 5 years. Fourteen cases(22.6%)experienced progression of visual field defects. There were differences in the history of diabetes and preoperative visual field staging between the two groups. The proportion of progressive cases in cases with diabetes was 46.2% compared to 16.3% in cases without diabetes(P=0.022). The percentage of progression of visual field defect was 38.9% in cases with mild preoperative visual field staging(stages 0-3)and 15.9% in cases with severe preoperative visual field staging(stages 4-5)(P=0.049). Conclusion Ab interno trabeculotomy with the Trabectome had a definite long-term efficacy. Some patients still had visual field defects progression after operation. Visual functional impairment of glaucoma should be considered during postoperative follow-up. Patients with diabetes and mild preoperative visual field stage were more likely to have visual field defects progression. The follow-up frequency of these patients should be increased and their visual field should be frequently monitored.

Anti-neutrophil cytoplasmic antibody associated vasculitis complicated with scleritis and cataract: a case study and literature review

LI Wanyu, GU Xuejun

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  149-152.  doi:10.6040/j.issn.1673-3770.0.2022.221

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Objective To investigate the clinical characteristics, diagnosis and treatment of antineutrophil cytoplasmic antibody(ANCA)associated vasculitis(AAV)complicated with scleritis and cataract. Methods Review the medical records of a 73-year-old female patient. One year after she was diagnosed as AAV in a foreign hospital, she was complicated with left eye scleritis, and the blurred vision in the left eye gradually worsened in the past six months. In our hospital, she was diagnosed as complicated cataract in the left eye, and she underwent phacoemulsification and intraocular lens implantation for cataract in the left eye. Results The corrected visual acuity was 0.3 on the first day after operation, and the anterior posterior segment was stable after 4 months of follow-up. Conclusion The clinical manifestations of AAV are complex and diverse, which is a group of rare diseases with potential vision threatening complications. The ANCA index of patients with vasculitis in the early or remission stage can be negative, and its titer will decrease when the disease is in remission, which can be used as an evaluation index to monitor the progress of the disease and judge the treatment effect. In terms of treatment, the combination of systemic drugs and early intervention of ophthalmology can reduce the degree of eye damage. The successful treatment of eye symptoms is usually based on effective systemic treatment, but sometimes the intervention of surgery is also necessary, and the selection of surgery and drug treatment are very important for the prognosis of the disease.

Research progress on the role and regulatory mechanism of group 2 innate lymphoid cells in chronic rhinosinusitis

CUI Ning, WANG Yunmeng, YANG Jingpu

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  153-159.  doi:10.6040/j.issn.1673-3770.0.2022.192

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Chronic rhinosinusitis is a chronic inflammatory disease that occurs in the mucosa of the sinuses, mainly manifested by nasal symptoms such as nasal congestion and runny nose, followed by head and facial swelling, and decreased or lost sense of smell. The course of disease is no less than 12 weeks. It is often complicated with respiratory diseases such as asthma and chronic obstructive pulmonary disease. As an inflammatory disease with a multifactorial etiology, it involves the immune system and epithelial barrier and is influenced by microbiota, environmental and genetic factors. Its pathogenesis is not yet clear. Innate lymphoid cells are the innate counterparts of T lymphocytes and lack adaptive antigen receptors generated by recombination of genetic factors. Among them, group 2 innate lymphoid cells(ILC2s)release large amounts of type 2 cytokines after activation, which is closely related to Th2 inflammation. This article reviews the role of ILC2s in chronic rhinosinusitis with nasal polyps and its regulatory mechanism, especially its interaction with regulatory T cells.

Review of pyroptosis molecular mechanism and applications in head and neck squamous cell carcinoma

YANG Yingling, GOU Haocheng, FENG Jun

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  160-165.  doi:10.6040/j.issn.1673-3770.0.2022.179

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Poor survival rates for cancer patients have led to further research on treatments to fight the disease. Programmed cell death(PCD)plays an important role not only in embryonic development, but also in occurrence and development of cancers. Pyroptosis is a type of PCD which has been receiving increasing attention for its dual role in tumors. This paper describes the molecular mechanisms of pyroptosis in terms of anti-cancer properties and aims to gain insight into its potential for cancer resistance. We also introduce related research on head and neck squamous cell carcinoma.

Research progress of pyroptosis in chronic airway inflammatory disease

YUAN Yue, FU Shengyao, JIANG Yan, CHEN Min

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  166-171.  doi:10.6040/j.issn.1673-3770.0.2022.197

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Pyroptosis is a form of programmed cell death that involves the activation of canonical(caspase-1-dependent)and noncanonical(caspase-4/5/11-dependent)pathways, which are normally triggered by inflammatory factors. Pyroptosis has become a trending discussion topic due to its role in promoting chronic inflammatory airway diseases, as revealed by previous studies. This paper reviews the latest research advances in pyroptosis, with respect to allergic rhinitis, chronic sinusitis, asthma, and chronic obstructive pulmonary diseases, with the aim of catalyzing new ideas for improved treatments.

Research progress of pyroptosis in senile degenerative diseases

ZHOU Jiamin, SONG Yuwan, SUN Yan

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  172-180.  doi:10.6040/j.issn.1673-3770.0.2022.090

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Pyroptosis is a process that mainly induces the activation of the inflammatory cysteine-aspartate-specific protease family through the inflammasome and subsequently cleaves the gasdermin family of pyroptotic proteins. This eventually leads to the rupture of cell membranes and release of cell contents, causing an intense novel programmed cell death mode of inflammatory responses. Currently reported pyroptosis pathways mainly include the caspase-1-dependent classical, caspase-11-dependent non-classical, caspase-3-dependent gasdermin E, and caspase-8-dependent gasdermin D pyroptosis pathways. In these multiple pyroptotic signaling pathways, the inflammasome and pyroptotic protein, gasdermins, play important roles as pioneers and executors. In recent years, with the advent of the aging era, research on pyroptosis in senile degenerative diseases has attracted attention. This article mainly reviews the main mechanism of pyroptosis and its research progress in senile degenerative diseases such as presbycusis, age-related macular degeneration, and Alzheimer's disease.

Research progress on the pathogenesis of posterior capsular opacification and on anterior capsular polishing

HAN Yiping, ZHANG Han

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  181-186.  doi:10.6040/j.issn.1673-3770.0.2022.112

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Posterior capsular opacification(PCO)is the most common postoperative complication of cataract surgery, and its occurrence and development are closely related to lens epithelial cells. Neodymium-doped yttrium aluminum garnet(Nd:YAG)laser posterior capsulotomy is a common method for the treatment of PCO. However, it has low universality and is associated with ocular complications. Therefore, the development of safe and effective strategies to prevent PCO remains a concern. This article reviews the pathogenesis of PCO and the technological progress of anterior capsular polishing in the clinical prevention of PCO.

Application progress of telemedicine in the management of glaucoma diagnosis and treatment

HE Meng, TANG Li

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  187-195.  doi:10.6040/j.issn.1673-3770.0.2022.135

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Glaucoma is a chronic progressive optic neuropathy that requires persistent follow-up. With the development and popularization of modern network communication technology and various smartphone communication platforms, information technology tools, such as web-based telemedicine(TM)platforms, provide convenient and efficient medical services to patients with chronic diseases. This allows the rational use of health resources, reduces medical expenses, and improves patient satisfaction. In recent years, web-based TM platforms have been used to diagnose and manage chronic diseases like glaucoma. The application of TM in the field of glaucoma includes disease screening, consultation and disease progress monitoring, and medical education. This article reviews the progress of TM in diagnosing and treating patients with glaucoma. This would serve as a reference for promoting and optimizing TM in managing patients with glaucoma.

A case report of a child with osteopetrosis diagnosed as strabismus

FENG Shijun, WANG Qi, ZHAO Bojun

Journal of Otolaryngology and Ophthalmology of Shandong University. 2023, 37(4):  196-200.  doi:10.6040/j.issn.1673-3770.0.2022.195

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