Objective: To identify factors that influence the severity of tinnitus via a hierarchical multiple linear regression model.Methods: The study was a retrospective cross-sectional analysis. The study included 331 patients experiencing tinnitus as their primary concern, who visited Shanghai Changzheng Hospital of the Navy Medical University between 2019 and 2021. Data on general health status and disease characteristics were collected from all patients. With their consent, participants underwent audiological evaluatons and completed questionnaires to analyze the characteristics of their tinnitus and the factors influencing its severity.Results: The correlation analysis showed a positive relationship between tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores with THI scores (P < 0.05) among nine examined variables (gender, handedness, employment status, age, BMI, tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores). The variables that were extracted from the multiple regression were; for the constant;β =-51.797,t = -4.484,P < 0.001, variable is significant; for the tinnitus loudness;β= 0.161,t = 2.604,P < 0.05, variable is significant; for the tinnitus frequency;β = 0.000,t= 1.269,P= 0.206, variable is not significant; for the SAS scores;β= 1.310,t = 7.685,P < 0.001, variable is significant; for the PSQI scores;β= 1.680,t = 5.433,P < 0.001, variable is significant. Therefore, the most accurate model for predicting severity in tinnitus patients is a linear combination of the constant, tinnitus loudness, SAS scores, and PSQI scores,Y (Tinnitus severity) =β0+β1(Tinnitus loudness) + β2(SAS scores) +β3(PSQI scores).β0,β1,β2, andβ3 are -51.797, 0.161, 1.310 and 1.680, respectively.Conclusion: Tinnitus severity is positively associated with loudness, anxiety levels, and sleep quality. To effectively manage tinnitus in patients, it is essential to promptly identify and address these accompanying factors and related symptoms.

Taste perception is one of the important senses in mammals. Taste dysfunction causes significant inconvenience in daily life, leading to subhealth and even life-threatening condition. Aging is a major cause to taste dysfunction, while the underlying feature related to gustatory aging is still not known. Using single-cell RNA Sequencing, differentially expressed genes between aged and young taste papillae are identified, including upregulated mt-Nd4l and Xist, as well as downregulated Hsp90ab1 and Tmem59. In the Tmem59-/- circumvallate papillae (CVP), taste mature cell generation is impaired by reduction in the numbers of PLCβ2+ and Car4+ cells, as well as decreases in expression levels of taste transduction genes. Tmem59-/- mice showed deficits in sensitivities to tastants. Through screening by GenAge and DisGeNET databases, aging-dependent genes and oral disease-associated genes are identified in taste papillae. In the CVP, aging promotes intercellular communication reciprocally between (cycling) basal cell and mature taste cell by upregulated Crlf1/Lifr and Adam15/Itga5 signaling. By transcriptional network analysis, ribosome proteins, Anxa1, Prdx5, and Hmgb1/2 are identified as transcriptional hubs in the aged taste papillae. Chronological aging-associated transcriptional changes throughout taste cell maturation are revealed. Aged taste papillae contain more Muc5b+ cells that are not localized in gustatory gland. Collectively, this study shows molecular and cellular features associated with taste papilla aging.

Abstract Objective Differentiating 2 types of chronic rhinosinusitis with nasal polyps (CRSwNP) is important for the treatment. The current diagnostic methods using single indicators, including peripheral blood eosinophils and traditional sinus computed tomography (CT) scores, are not accurate. In this study, we aimed to investigate the diagnostic value of combining peripheral blood eosinophils and improved sinus CT scores for eosinophic chronic rhinosinusitis (ECRS). Study Design Retrospective cohort. Setting Tertiary medical center. Methods We conducted a study involving 81 patients with CRSwNP. Peripheral blood samples were collected from the non‐ECRS and ECRS groups. Improved three‐dimensional volume image analysis and Lund‐Mackay scoring system were performed to quantify the thickening of sinus mucosa. Multivariate binary logistic regression analysis was carried out to detect the predictive value of the scoring indicators. For significant indexes, receiver operating characteristic (ROC) curve analysis was applied. Results The ECRS group had higher levels of blood eosinophil percentage and count, ethmoid sinus score, total sinus score, the ratio of ethmoid sinus score and maxillary sinus score, and the difference between ethmoid and maxillary score, compared to the non‐ECRS group (P < 0.05). Binary logistic regression analysis demonstrated that both blood eosinophil percentage and the improved E − M score (subtraction of ethmoid and maxillary sinus scores) were significant predictors of ECRS diagnosis (P < .01). ROC curve analysis indicated that the combination of improved E − M score and blood eosinophil percentage had a higher diagnostic value compared to either factor alone (area under the curve = 0.874). Conclusion Our study suggested the combination of improved total ethmoid sinus‐maxillary score and blood eosinophil percentage is more accurate in predicting the diagnosis of ECRS.

Background: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. Objective: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. Methods: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. Results: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. Conclusions: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions. (J Allergy Clin Immunol 2024;154:644-56.)

Chalcones are typically privileged scaffolds found in many naturally occurring compounds. They are widely used as lead compounds for designing novel bioactive molecules with a series of potential pharmacologic activities. This review highlights evidence of chalcone as a privileged scaffold in medicinal chemistry as an update of our comprehensive review (Chem. Rev. 2017; 117, 7762–7810). The simple chalcones according to Michael acceptor-related mechanisms (e.g., IκB kinases, thioredoxin reductase, and the Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–antioxidant response element pathway) are principally classified. Representative hybrid chalcones are emphasized, including fused hybrid chalcones and linked hybrid chalcones. Moreover, future challenges and perspectives are provided to facilitate the development of chalcone derivatives in the medicinal chemistry community.

Objective:To discuss and summarize the causes，clinical manifestations，treatments，as well as diagnosis and treatment experience of deep neck severe suppurative inflammation complicated by sepsis，and to provide diagnosis and treatment ideas for the diagnosing and treating post-traumatic neck infectious diseases under the conditions of medical support in wartime.Methods:The medical records of 16 patients with sepsis complicated by deep neck severe suppurative inflammation treated in the department of otolaryngology of Changzheng Hospital of Naval Medical University from January 2018 to January 2022 were reviewed，including the general information，cause of onset，main symptoms，imaging data，treatments，pathogen culture，course of disease，and data of follow-up. The features of disease and diagnosis and treatment schemes were summarized. Furthermore，according to the relevant reports of neck injury on battlefield，the diagnosis and treatment measures of neck suppurative inflammation complicated by sepsis in wartime were analyzed.Results:Among the 16 patients，seven complicated by diabetes，of whom two had poor blood glucose control due to irregular antidiabetic drug use；while the rest nine patients had no history of diabetes. Through comparison between the two groups，it was found that the diabetes patients had a longer disease course than the patients without diabetes，with a statistically significant difference（ P=0.010 7）. Among all the patients，most of the cause of onset were upper respiratory tract infection（37.5%）and pharyngeal foreign body（37.5%）；the cases with trauma（12.5%）and odontogenic infection（12.5%）as cause of onset were often complicated by diabetes. Fever（100%）and sore throat（68.75%）were the main symptoms. In addition，a number of patients also had neck mass（18.75%），dysphagia（25%），and dyspnea（12.5%）. Seven patients underwent puncture drainage and nine patients underwent incision drainage. G + cocci were the most common pathogens in postoperative pus（including Streptococcus viridis， Staphylococcus aureus， Streptococcus pharyngitis，and Streptococcus pneumoniae，accounting for 37.5%），followed by Klebsiella pneumoniae（18.75%）. The patients without history of diabetes had no serious complications. Four cases with serious complications were well-controlled by active symptomatic treatment. None of the patients died during the follow-up，among whom 14 cases（81.25%）were cured and two cases had poor curative effect；one of the two cases was in deep coma during the follow-up，and the other suffering from poor blood glucose control and repeated abscess had no recurrence during the follow-up. Conclusion:Deep neck severe suppurative inflammation complicated by sepsis is a great challenge for clinicians due to its confusing early symptoms and the lethality of critical complications. Under limited conditions of battlefield medical support，the rapid diagnosis and treatment of secondary infection after neck trauma is even more challenging. Therefore，it is of great significance to improve medical support in both peacetime and wartime by studying and analyzing the series of cases with similar clinical critical conditions，further improving the clinical diagnosis and treatment pathway，and shortening the cure time of patients as much as possible.

表皮样囊肿,又称角质囊肿,多发生于皮肤外胚层,内含皮肤鳞状上皮细胞及类脂质,可先天发生,也可因外伤、手术使上皮细胞或附属器卷入至皮下所致,主要表现为生长缓慢、质地坚硬的圆形肿物[1].据Sanglee等[2]报道,表皮样囊肿在头颈部的发生率为1.6％～6.9％,在鼻眶颅底肿瘤中则罕见,临床上以手术切除为首选.本文报道1例鼻眶颅沟通性巨大表皮样囊肿,旨在提高对此病的认识,对于有症状或无症状但颅底受侵犯的表皮样囊肿建议尽早手术切除,并修复重建颅底,避免引起相关并发症.

OBJECTIVE:We aimed to evaluate the effectiveness of topical tranexamic acid (TXA) versus topical vasoconstrictors in the management of epistaxis via a systematic review and meta-analysis.METHODS:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for the meta-analysis. We systematically searched Embase, Web of Science, Cochrane Library, CNKI, and PubMed for randomized controlled trials (from inception to August 2022; no language restrictions), comparing the effect of topical TXA and topical vasoconstrictors on the treatment of epistaxis. The Q test was used to evaluate heterogeneity, and funnel plots were utilized to identify bias. For the meta-analysis, the fixedeffects model was employed, and the t-test was utilized to determine significance.RESULTS:Of 1012 identified studies, 5 were found to be eligible for our analysis. In total, 598 patients were included; 297 of them received TXA and 301 received vasoconstrictors. Hemostasis was more likely to be achieved at the first re-assessment in patients treated with TXA. Subgroup analysis indicated patients treated with TXA to have less likelihood of bleeding recurrence, compared to patients treated with vasoconstrictors. The detected time interval of rebleeding was 10 min, between 24 h to 72 h, and after 7 days, respectively, and the differences were significant between the two groups of patients treated with TXA and vasoconstrictors.CONCLUSION:Topical TXA was associated with better post-treatment hemorrhagic arrest rates compared to topical vasoconstrictors in the management of epistaxis.

Proteolysis-targeting chimeras (PROTACs) is a fast-growing technology providing many strengths over inhibition of protein activity directly and is attracting increasing interest in new drug discovery and development. However, efficiently identifying potent and drug-like degraders is still challenging in the development of PROTACs. Complementary to traditional PROTACs, several emerging types of PROTACs, such as homobivalent PROTACs based on two E3 ligases (e.g., CRBN, VHL, MDM2, TRIM24), chemical-or biological-based trivalent/multitargeted PROTACs, and covalent PROTACs, are rising for targeted protein degradation. These new types of PROTACs have several advantages over the traditional PROTACs including high selectivity, low toxicity, better therapeutic effects, and so on. In this perspective, we will summarize the latest development of representative PROTACs focusing on research mainly in past 10 years and discuss their advantages and disadvantages. Moreover, the outlook and perspectives on the associated challenges and future directions will be provided.

Objective To investigate the characteristics of sleep disorders and anxiety in patients with tinnitus, their influencing factors, and the role of sleep disorders as mediators. Methods The general conditions and disease characteristics of 393 patients with tinnitus presented to the Changzheng Hospital of the Naval Medical University from 2018 to 2021 were collected. All patients accepted questionnaires such as Tinnitus Handicap Inventory (THI), Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS), and then the characteristics and the influencing factors of sleep disorders and anxiety were analyzed. Results Among the 393 tinnitus patients, 213 cases (54.19%) were diagnosed with sleep disorders, and 78 cases (19.85%) were diagnosed with anxiety, including 25 men (32.1%) and 53 women (67.9%). Binary regression showed that gender, hearing loss, tinnitus severity, and sleep disorders severity were positively associated with anxiety. Multiple logistic regression analysis showed that female gender (OR = 2.526, P = 0.008), hearing loss (OR = 2.901, P = 0.003, tinnitus severity (OR = 1.863, P = 0.003) and sleep disorders (OR = 2.510, P = 0.001) were the independent risk factors of anxiety. The mediating effect of sleep disorders between tinnitus severity and anxiety accounted for 27.88% of the total effect size. Conclusion Females patients with hearing loss, moderate to severe tinnitus, and sleep disorders were at greater risk for anxiety, with sleep disorders partially mediating the anxiety associated with tinnitus.