A cross-sectional study on predictors of patients' tinnitus severity.

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; ß = -51.797, t = -4.484, P < 0.001, variable is significant; for the tinnitus loudness; ß = 0.161, t = 2.604, P < 0.05, variable is significant; for the tinnitus frequency; ß = 0.000, t = 1.269, P = 0.206, variable is not significant; for the SAS scores; ß = 1.310, t = 7.685, P < 0.001, variable is significant; for the PSQI scores; ß = 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) = ß 0 + ß 1 (Tinnitus loudness) + ß 2 (SAS scores) + ß 3 (PSQI scores). ß 0, ß 1, ß 2, and ß 3 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.

Eosinophil extracellular traps in respiratory ailment: Pathogenic mechanisms and clinical translation.

Background: Eosinophilic extracellular traps (EETs) are reticular complexes comprising deoxyribonucleic-Acid (DNA) fibers and granule proteins. Aims: EETs play a crucial role in antimicrobial host responses and are pathogenic when overproduced or under degraded. EETs created by eosinophils appear to enable vital immune responses against extra-cellular pathogens, nevertheless, trap overproduction is evident in pathology. Materials & Methods: As considerably research is performed, new data affirmed that EETs can alter the outcome of respiratory ailment. Results: We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation. Discussion: Whether EETs can be used as a prospective brand-new target for the diagnosis, treatment and prognosis of respiratory ailments is a scientific theme worth studying. Conclusion: We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation.

Analysis of Diagnosis and Treatment Strategies for Parapharyngeal Space Tumors With Follicular Dendritic Sarcoma.

BACKGROUND: Parapharyngeal space tumor is a tumor that occurs in the parapharyngeal space. Parapharyngeal space tumors are uncommon, accounting for about 0.5% of head and neck tumors. Eighty percent of them are benign and 20% are malignant. The pathologic types of tumors are varied, mainly neurogenic tumors and salivary gland tumors. Follicular dendritic sarcomas are much rarer, with an inert biological behavior and a low-grade malignant sarcoma. Clinicians face difficulties in the management of this lesion. Therefore, a comprehensive analysis of the management of this disease is necessary. CASE PRESENTATIONS: In May 2023, a 22-year-old male presented with pharyngeal discomfort, dysphagia, and sleep apnea. The patient underwent MRI which showed a rounded hypodense shadow with a size of 3.2×2.1×4.5 cm in the left lateral pharyngeal wall and a mass located in the posterior aspect of the left submandibular gland. After preliminary diagnosis of left parapharyngeal space tumor and left neck mass, the clinician performed transoral endoscopy-assisted resection of the left parapharyngeal space tumor and transcervical resection of the left cervical mass. The patient has been followed up without recurrence. CONCLUSIONS: This case provided a reference for the diagnosis and management of parapharyngeal space tumors. In particular, new insights into the diagnosis and management of a rare pathologic type were presented, which had the potential to improve the overall understanding of this disease.

Single-cell transcriptomic atlas of taste papilla aging.

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 PLCß2+ 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.

A single-cell transcriptomic census of mammalian olfactory epithelium aging.

Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.

DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells.

Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine Dmxl2, whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave I amplitude of the auditory brainstem response. Membrane capacitance measurements of the IHCs revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of SVs and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the SVs.

The value of T1- and FST2-Weighted-based radiomics nomogram in differentiating pleomorphic adenoma and Warthin tumor.

PURPOSE: To establish a radiomics nomogram based on MRI radiomics features combined with clinical characteristics for distinguishing pleomorphic adenoma (PA) from warthin tumor (WT). METHODS: 294 patients with PA (n = 159) and WT (n = 135) confirmed by histopathology were included in this study between July 2017 and June 2023. Clinical factors including clinical data and MRI features were analyzed to establish clinical model. 10 MRI radiomics features were extracted and selected from T1WI and FS-T2WI, used to establish radiomics model and calculate radiomics scores (Rad-scores). Clinical factors and Rad-scores were combined to serve as crucial parameters for combined model. Through Receiver operator characteristics (ROC) curve and decision curve analysis (DCA), the discriminative values of the three models were qualified and compared, the best-performing combined model was visualized in the form of a radiomics nomogram. RESULTS: The combined model demonstrated excellent discriminative performance for PA and WT in the training set (AUC=0.998) and testing set (AUC=0.993) and performed better compared with the clinical model and radiomics model in the training set (AUC=0.996, 0.952) and testing model (AUC=0.954, 0.849). The DCA showed that the combined model provided more overall clinical usefulness in distinguishing parotid PA from WT than another two models. CONCLUSION: An analytical radiomics nomogram based on MRI radiomics features, incorporating clinical factors, can effectively distinguish between PA and WT.

Structure-Activity Relationship Study of (E)-3-(6-Fluoro-1H-indol-3-Yl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (FC116) Against Metastatic Colorectal Cancers Resistant to Oxaliplatin.

Advanced metastatic colorectal cancer (mCRC) and the development of drug resistance to chemotherapy pose significant challenges in clinical settings. In previous studies, we have demonstrated the potent cytotoxic activity of (E)-3-(6-fluoro-1H-indol-3-yl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (FC116) and related 30 derivatives against mCRC by targeting microtubules. In this study, we aimed to evaluate the efficacy of the 31 compounds and explore the structure-activity relationship (SAR) against oxaliplatin-resistant mCRC. We found that most of the derivatives showed high sensitivity toward the oxaliplatin-resistant HCT-116/L cells. Particularly, FC116 exhibited a better GI50 value against the resistant mCRC cell line, HCT-116/L, compared to standard therapies. We also observed a safer therapeutic window for FC116 and a synergistic effect when it was used in combination with oxaliplatin. Mechanistically, FC116 induced the G2/M phase arrest by downregulating cyclin B1 expression through its interaction with microtubules in resistant colorectal cancer cells. Furthermore, in vivo experiments demonstrated that FC116 significantly suppressed tumor growth, achieving a 78% reduction at a dose of 3 mg/kg, which was superior to the 40% reduction achieved by oxaliplatin treatment. Overall, our findings suggest that the indole-chalcone compound FC116 represents a promising lead for chemotherapy in oxaliplatin-resistant mCRC.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

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.

Infratemporal Fossa Schwannoma Surgery via a Combined Prelacrimal Recess, Caldwell-Luc, and Distal Intraoral Approach.

BACKGROUND: The deep location of infratemporal fossa (ITF) combined with the abundant vascular plexus in it increased the difficulty of removing the mass in ITF through endoscope surgery approach. However, under appropriate circumstances, the excision of ITF tumors through a combined prelacrimal recess, Caldwell-Luc, and distal intraoral approach can be safely performed with minimal impact on the surrounding tissues. CASE PRESENTATION: The Department of Neurology received a 69-year-old male patient who had been experiencing headache, dizziness, and numbness from the mastoid region of his left ear to the corner of his mouth for a duration of 22 days. Cranial magnetic resonance imaging revealed the presence of a tumor located in the ITF. Following transfer to our department, surgical intervention was performed using a combined approach involving the prelacrimal recess, the anterior wall of maxillary sinus, and lateral ITF to successfully remove the tumor. Postoperative pathologic examination confirmed schwannoma as its nature. The patient was discharged in excellent condition without any functional impairment. CONCLUSIONS: On the basis of this case, the authors believe that this combined approach can offer a distinct endoscopic perspective and adequate surgical workspace, which is crucial for tumor removal while preserving the integrity of surrounding normal tissues. Moreover, the utilization of multiple small incisions has minimal impact on postoperative recovery.

Gut microbiota and chronic rhinosinusitis: a two-sample Mendelian randomization study.

BACKGROUND: The nasal cavity and gut are interconnected, both housing a rich natural microbiome. Gut microbiota may interact with nasal microbiota and contribute to the development of chronic rhinosinusitis (CRS). However, the specific role of gut microbiota in CRS has not been fully investigated. Therefore, we conducted a two-sample Mendelian randomization study to reveal the potential genetic causal effect of gut microbiota on CRS. METHODS: We performed a two-sample Mendelian Randomization (MR) analysis using aggregated data from genome-wide association studies (GWAS) on gut microbiota and CRS. The primary method used to assess the causal relationship between gut microbiota and CRS was the inverse variance weighting (IVW) method. In addition, sensitivity analyses were conducted to evaluate the robustness of the MR results, including heterogeneity, pleiotropy, and leave-one-out tests. RESULTS: Genetically predicted twelve gut microbiota, including class Coriobacteriia, class Methanobacteria, family Coriobacteriaceae, family Methanobacteriaceae, family Pasteurellaceae, genus Haemophilus, genus Ruminococcus torques group, genus Subdoligranulum, order Coriobacteriales, order Methanobacteriales, order Pasteurellales, and phylum Proteobacteria, demonstrated a potential inhibitory effect on CRS risk (P < 0.05). In addition, four gut microbiota, including family Streptococcaceae, genus Clostridium innocuum group, genus Oscillospira, and genus Ruminococcaceae NK4A214 group, exhibited a causal role in increasing CRS risk (P < 0.05). Sensitivity analyses showed no evidence of heterogeneity or pleiotropy (P > 0.05). CONCLUSIONS: This study reveals the causal relationship between specific gut microbiota and CRS, which provides a new direction and theoretical foundation for the future development of interventions and prevention and treatment strategies for CRS.

Analysis of Diagnosis and Treatment Strategies for Primary Juvenile Psammomatoid Ossifying Fibroma Complicated With Primary Aneurysmal Bone Cyst.

BACKGROUND: Juvenile Psammomatoid Ossifying Fibroma (JPOF) is a type of noncancerous bone tumor that usually affects adolescents in the craniomaxillofacial area. Clinical manifestations are usually symptoms caused by the tumor's invasive compression of surrounding tissues. Aneurysmal Bone Cyst (ABC) is also a benign bone tumor, and it typically occurs in long bones and the spine. Only 2% to 3% of cases occur in the head and neck. Due to the rarity of this combination of clinical cases, clinicians face difficulties in comprehensively understanding this complex lesion. Therefore, a comprehensive review of the clinical manifestations and characteristic imaging findings is necessary for surgeons. CASE PRESENTATIONS: On April 6, 2019, a 13-year-old boy presented with left maxillofacial bulge and pain for 1 month. Magnetic resonance imaging of the paranasal sinuses showed an irregular hive-like mass signal in the left maxillary sinus, and cystic changes with fluid levels were seen in the lesion. After the initial diagnosis of JPOF with primary ABC, we decided to perform a facial mid-facial resection of maxillary sinus tumor to remove the tumor tissue. Finally, after 3 recurrences and 4 operations, there was no tumor recurrence for 20 months after the last operation, and the patient was still under continuous follow-up. CONCLUSIONS: This case provided a reference for the diagnosis and treatment of JPOF combined with ABC. In particular, a new understanding of the association between the two diseases and the management of recurrence were proposed, which had the potential to improve clinical understanding of this complicated condition.

Blood Eosinophil Percentage and Improved Sinus CT Score as Diagnostic Tools for ECRS.

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.

Identification and analysis of lipid metabolism-related genes in allergic rhinitis.

BACKGROUND: Studies have shown that the lipid metabolism mediator leukotriene and prostaglandins are associated with the pathogenesis of allergic rhinitis (AR). The aim of this study was to identify key lipid metabolism-related genes (LMRGs) related to the diagnosis and treatment of AR. MATERIALS AND METHODS: AR-related expression datasets (GSE75011, GSE46171) were downloaded through the Gene Expression Omnibus (GEO) database. First, weighted gene co-expression network analysis (WGCNA) was used to get AR-related genes (ARRGs). Next, between control and AR groups in GSE75011, differentially expressed genes (DEGs) were screened, and DEGs were intersected with LMRGs to obtain lipid metabolism-related differentially expressed genes (LMR DEGs). Protein-protein interaction (PPI) networks were constructed for these LMR DEGs. Hub genes were then identified through stress, radiality, closeness and edge percolated component (EPC) analysis and intersected with the ARRGs to obtain candidate genes. Biomarkers with diagnostic value were screened via receiver operating characteristic (ROC) curves. Differential immune cells screened between control and AR groups were then assessed for correlation with the diagnostic genes, and clinical correlation analysis and enrichment analysis were performed. Finally, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was made on blood samples from control and AR patients to validate these identified diagnostic genes. RESULTS: 73 LMR DEGs were obtained, which were involved in biological processes such as metabolism of lipids and lipid biosynthetic processes. 66 ARRGs and 22 hub genes were intersected to obtain four candidate genes. Three diagnostic genes (LPCAT1, SGPP1, SMARCD3) with diagnostic value were screened according to the AUC > 0.7, with markedly variant between control and AR groups. In addition, two immune cells, regulatory T cells (Treg) and T follicular helper cells (TFH), were marked variations between control and AR groups, and SMARCD3 was significantly associated with TFH. Moreover, SMARCD3 was relevant to immune-related pathways, and correlated significantly with clinical characteristics (age and sex). Finally, RT-qPCR results indicated that changes in the expression of LPCAT1 and SMARCD3 between control and AR groups were consistent with the GSE75011 and GSE46171. CONCLUSION: LPCAT1, SGPP1 and SMARCD3 might be used as biomarkers for AR.

Cisplatin attenuates taste cell homeostasis and induces inflammatory activation in the circumvallate papilla.

Rationale: Gustation is important to several biological functions in mammals. However, chemotherapy drugs often harm taste perception in cancer patients, while the underlying mechanism is still unclear for most drugs and there is no effective way to restore taste function. This study investigated the effects of cisplatin on the taste cell homeostasis and gustatory function. Methods: We used both mice and taste organoid models to study the effect of cisplatin on taste buds. Gustometer assay, gustatory nerve recording, RNA-Sequencing, quantitative PCR, and immunohistochemistry was performed to analyze the cisplatin-induced alteration in taste behavior and function, transcriptome, apoptosis, cell proliferation and taste cell generation. Results: Cisplatin inhibited proliferation and promoted apoptosis in the circumvallate papilla, leading to significant impairment in taste function and receptor cell generation. The transcriptional profile of genes associated with cell cycle, metabolic process and inflammatory response was significantly altered after cisplatin treatment. Cisplatin inhibited growth, promoted apoptosis, and deferred taste receptor cell differentiation in taste organoids. LY411575, a γ-secretase inhibitor, reduced the number of apoptotic cells and increased the number of proliferative cells and taste receptor cells, potentially suggesting as a taste tissue protective agent against chemotherapy. LY411575 treatment could offset the increased number of Pax1+ or Pycr1+ cells induced by cisplatin in the circumvallate papilla and taste organoids. Conclusion: This study highlights the inhibitory effects of cisplatin on taste cell homeostasis and function, identifies critical genes and biological processes regulated by chemotherapy, and proposes potential therapeutic targets and strategy for taste dysfunction in cancer patients.

A Systematic Review and Meta-analysis of the Effects of Topical Tranexamic Acid versus Topical Vasoconstrictors on the Management of Epistaxis.

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.

Profiling of the chemical space on the phenyl group of substituted benzothiazole RIPK3 inhibitors.

Necroptosis is confirmed as a precisely programmed cell death that is activated in caspase-deficient conditions. Receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed-lineage kinase domain-like pseudokinase (MLKL) are the key regulators involved in the signaling pathway. However, accumulating evidence suggests that RIPK1 also works in apoptosis and inflammation pathways independent of necroptosis. Differently, RIPK3 signals necroptosis independent of RIPK1. Thus, identification of specific RIPK3 inhibitors is of great importance for the drug development associated with necroptosis. The benzothiazole carboxamide is a privileged scaffold as RIPK3 inhibitors developed by our group recently. In this study, we work on the phenyl group in-between of benzothiazole and carboxamide to profile the chemical space. Finally, a chlorinated derivative XY-1-127 was found to specifically inhibit necroptosis rather than apoptosis with an EC50 value of 676.8 nM and target RIPK3 with a Kd of 420 nM rather than RIPK1 (Kd = 4300 nM). It was also confirmed to block the formation of necrosome by inhibiting RIPK3 phosphorylation at 1 µM in necroptosis cells. This work discovers the chemical space insights on the phenyl group of the substituted benzothiazole RIPK3 inhibitors and provides a new lead compound for further development.

Multidisciplinary Team in Severe Infectious Complications Caused by Pharyngeal Foreign Body.

BACKGROUND: Pharyngeal foreign body is not only a common emergency in people's daily life, but also a common simple disease in otorhinolaryngology. However, the disease is easy to be ignored due to its common occurrence, which may lead to a series of serious complications including sepsis and local abscess. CASE PRESENTATION: In this case, a patient with sepsis, piriform fistula, deep neck abscess, and mediastinal abscess caused by a fishbone was reported. After reviewing the international literature on severe infectious complications caused by foreign bodies in pharynx, the authors emphasize the important role of multidisciplinary team in dealing with complex complications. RESULT: The whole process of patient from onset to recovery was summarized in a timeline. During hospitalization, the value of leukocyte counts and C-reactive protein in routine blood test was record dynamically. The electronic laryngoscopy, neck computed tomography and chest computed tomography were used to judge treatment efficacy. After about 2 months of hospitalization, the patient was recovered without sequelae. No adverse reactions were found during the follow-up. CONCLUSION: The incorrect method of removing foreign body after mis-swallowing may develop serious complications. Therefore, It is important to strengthen medical preaching for general population of correct treatments after foreign body ingestion. In addition, the case reminds clinicians to pay more attention to patients' medical history and details of all medical examinations, which may provide significant clues for making the correct diagnosis and treatment quickly.

Associations between sleep disorders and anxiety in patients with tinnitus: A cross-sectional study.

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.