A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss.

OBJECTIVES: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. METHODS: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. RESULTS: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. CONCLUSION: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss. LEVEL OF EVIDENCE: Level 4.

Gene expression profiles of mRNA, lncRNA, miRNA, and circRNA and their clinical implications in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with complex pathophysiology and therapeutic strategies. Moreover, the molecular mechanisms underlying the pathogenesis of CRSwNP are incompletely understood. OBJECTIVE: This study aimed to investigate the transcriptomic characteristics, ceRNA networks, and whether these molecular markers play a role in the occurrence and development of CRSwNP. METHODS: Following RNA sequencing, a ceRNA network was predicted and constructed based on the sequencing results and multiple databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) were applied to analyze the potential mechanisms in relation to the pathogenesis of CRSwNP. CIBERSORT was used to evaluate the immune cell infiltration levels in CRSwNP. The candidate genes of differentially expressed (DE) mRNA, DE-lncRNA, DE-miRNA, and DE-circRNA were verified by RT-qPCR, and the back-splice junction of circRNA was verified using Sanger sequencing. The clinical significance of differentially expressed genes was analyzed with correlation test and receiver operating characteristic curve. RESULTS: We identified 716 DE-mRNA, 230 DE-lncRNA, 42 DE-miRNA, and 46 DE-circRNA, and GO and KEGG enrichment analyses indicated that they were involved in multiple biological pathways, predominantly those associated with immunity and inflammation. DO analysis revealed CRSwNP is associated with diseases such as gastroesophageal reflux and allergic reactions. High expression of circ_0021727 was significantly and positively correlated with several important clinical indicators, and the area under the curve was 0.741. CONCLUSIONS: This study provides transcriptomic characteristics, which are potential biomarkers or therapeutic targets for the diagnosis and treatment of CRSwNP.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Abstract Introduction: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Generation of Fused Seven-Membered Polycyclic Systems via Ring Expansion and Application to the Total Synthesis of Sesquiterpenoids.

Seven-membered polycyclic architectures, widely present in natural products and molecular drugs, are challenging synthetic targets. However, methods for synthesizing fused medium-sized bicyclo[m.n.0] ring systems, including the benzo-cycloheptane systems, are still urgent. Herein we describe a base-induced ring expansion as a general strategy to construct a wide range of fused seven-membered ring systems. The application of this method was demonstrated by the efficient total syntheses of two sesquiterpenoids, plecarpenene and plecarpenone, both bearing a fused bicyclo[5.3.0]decane skeleton.

Onodi cell mucocele with cholesterol granuloma is more likely to cause serious optic neuropathy, compared with simple Onodi cell mucocele.

OBJECTIVE: The objective is to describe the clinical features, treatments, and outcomes of a case series of patients with Onodi cell mucocele, with or without cholesterol granuloma (CG). MATERIAL AND METHODS: We retrospectively reviewed the medical records of eight patients diagnosed with Onodi cell mucocele at a single tertiary care university hospital in Beijing, China, between January 2017 and September 2020. Data regarding nasal symptoms, ocular symptoms, sinus computed tomography findings, treatments, histopathological results, and clinical outcomes were extracted. RESULTS: We identified eight patients (six men and two women) of an average age of 48.1 (range, 26-70) years. Four patients presented nasal symptoms. Three patients presented ocular symptoms. Among them, one patient experienced concurrent nasal and ocular symptoms. Two patients were diagnosed based on a physical examination in the absence of nasal or ocular symptoms. All patients underwent endoscopic sinus surgery. The pathological specimens showed mucocele in four cases and mucocele with CG in the other four cases. Among the four cases with CG, three cases presented with decreased vision. After endoscopic sinus surgery, one patient recovered completely, and two patients showed significant improvement. CONCLUSION: If Onodi cell opacity is observed, especially with optic neuropathy, mucocele and CG are important differential diagnoses. The combination of mucocele and CG is more likely to promote bone destruction and cause serious optic neuropathy than simple mucocele. Endoscopic sinus surgery is appropriate. Diagnoses, treatments, and follow-up should be performed by a multidisciplinary team.

Clinical features in maxillary sinus fungus ball in patients with malignant hematological disease.

PURPOSE: Previous studies on fungus balls have primarily focused on immunocompetent patients, and only a few studies have described the clinical characteristics of fungus balls in malignant hematological disease (MHD) patients. Therefore, we compared the clinical features of maxillary sinus fungus ball (MSFB) between immunosuppressive patients with MHD and immunocompetent patients. METHODS: Twenty patients with MHD and 40 randomly selected immunocompetent patients were enrolled and divided into MHD and non-MHD groups. All patients were diagnosed with MSFB and their clinical features were retrospectively analyzed. RESULTS: Patients in the MHD group had non-specific clinical symptoms and endoscopic manifestations of MSFB, similar to those in the non-MHD group. On computed tomography (CT), the MHD group showed higher Lund-Mackay scores, lesser single sinus opacifications, more multiple sinus opacifications on the affected side, and more bilateral opacifications compared to the non-MHD group. The MHD group had a lower frequency of central hyper-density and heterogeneous opacifications than the non-MHD group. There were no significant differences between the two groups in terms of the fungal-infected side, lateral sinus wall ratio, sclerosis of the lateral sinus wall, erosion of the inner sinus wall, and nasal septum deviation. CONCLUSION: The clinical symptoms and endoscopic manifestations of MSFB in patients with MHD were similar to those of immunocompetent patients. However, more atypical signs and wider mucosal inflammation were found on CT scans of MSFB patients with MHD. These results indicate that caution should be executed when excluding the possibility of fungus balls in immunosuppressive patients.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea.

INTRODUCTION: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. OBJECTIVE: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. METHODS: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. RESULTS: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1ß, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. CONCLUSION: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

Comparison Between Multiple and Solitary Fungus Balls: A Retrospective Analysis.

OBJECTIVES: The most common type of noninvasive fungal rhinosinusitis is fungus ball (FB), which usually involves a solitary paranasal sinus. Multiple fungus balls (MFBs) are rarely reported in literature. The purpose of this study was to analyze and compare the clinical features of MFBs and solitary fungus ball (SFB). METHODS: We retrospectively investigated consecutive cases of FB between 2001 and 2018 and compared the clinical records of SFB with MFBs with respect to demographics, clinical features, location, radiological findings, and operative outcome. RESULTS: A total of 440 SFB and 43 MFBs cases were included in the study. The mean age was 55.3 ± 13.3 and 60.6 ± 10.9 years, respectively (P = .011). The incidence of MFBs obviously increased from 2001 to 2018. The clinical symptoms and laboratory examination were similar. On computed tomography images, complete opacification, septal deviation, Haller cells, and obstruction of ostiomeatal complex were more common (P < .05). The incidence of SFB on the left and right sides was similar, while MFBs were seen to involve both sides in 74.4%. CONCLUSIONS: Compared with SFB, MFBs showed some special characteristics. The MFBs affected older patients showed wide range of lesions and complex anatomy. Surgical technique is very important. Much more attention should be paid to this not so uncommon disease during the perioperative period.

Computed Tomography Analysis of the Anterosuperior Portion of the Bulla Lamella in Chinese Subjects and Its Surgical Significance in Endoscopic Frontal Sinusotomy.

INTRODUCTION: The anterosuperior portion of the bulla lamella can extend into the frontal sinus and form the supra bulla frontal cell (SBFC) and supraorbital ethmoid cell (SOEC). This can affect the frontal drainage pathway and make surgery more challenging. OBJECTIVES: The aim of the study was to compare the anatomical characteristics of SBFC and SOEC in Chinese chronic rhinosinusitis (CRS) patients and explore the relationship between the cells and frontal sinusitis (FS). The surgical skills in dealing with these cells were also studied. METHODS: We prospectively identified SBFC and SOEC in 114 patients with CRS by computed tomography (CT). The sides of the patients were divided into groups A (with FS) and B (without FS). CT scans were analyzed to distinguish the SBFC, SOEC, and the drainage pathway. Statistical analysis was conducted to determine whether the cells were associated with the occurrence of FS. RESULTS: The prevalence of frontal cells was as follows: SBFC: 9.65%, SOEC: 21.93%. There was an association between the presence of SBFC and FS (p < 0.05). The anterior drainage pathway was present in patients with SBFC and SOEC, anterolateral pathway in those with SBFC/SOEC coexisting with the frontal septal cell, and anteromedial pathway in those with SBFC/SOEC coexisting with the supra agger frontal cell. CONCLUSIONS: There was an association between the presence of SBFC and the occurrence of FS. Extension of the anterosuperior portion of the bulla lamella into the frontal sinus obstructed the drainage pathway posteriorly. Understanding the anatomy may help surgeons thoroughly dissect the bulla lamella.

Artemisia Annua sublingual immunotherapy for seasonal allergic rhinitis: A multicenter, randomized trial.

BACKGROUND: Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. METHODS: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. RESULTS: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 ± 0.52 vs 1.95 ± 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically Artemisia annua monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious. CONCLUSION: This study indicates that SLIT with Artemisia annua drops is an effective and safe treatment option in Chinese patients with Artemisia Annua-induced AR.

Accidental migration of a dental implant into the nasal cavity.

The accidental migration (i.e., displacement) of dental implants into the maxillary sinus is a relatively common complication in dental clinical practice. Here, we report the extremely rare nasal cavity migration of a dental implant in a 23-year-old man. Considering the superficial location of the dental implant and the absence of oronasal fistula formation, we attempted to remove the implant via endoscopy, nasal bayonet forceps, curved hooks, and suction in an ambulatory surgery setting with the patient under local anesthesia. Importantly, we were able to extract the implant with only minor complications. The patient received medication for 2 weeks and exhibited uneventful healing. Our findings may be useful for physicians and dentists who encounter similar situations in clinical practice.

Correction to: Efficacy and safety of delivery of topical medication on to the frontal sinus at different head positions after frontal sinusotomy.

In the original publication of the article, under the experimental protocol of the section "Clinical head position study in postoperative CRS patients", the following sentence "There were 20 CRS patients, 12 male and 8 female across an age range of 19-64 years…" was published incorrectly.

Efficacy and safety of delivery of topical medication on to the frontal sinus at different head positions after frontal sinusotomy.

PURPOSE: Effective topical medications delivery to the frontal sinus is crucial to recovery from frontal sinusotomy. However, finding a way to deliver local medications to the frontal sinus is still a major challenge. The objective of this study was to evaluate the influence of various head positions on postoperative frontal sinus drug deposition. The safety and efficacy were also evaluated in postoperative chronic rhinosinusitis (CRS) patients. METHODS: Full house surgery was performed on six fresh frozen cadaver heads. The fluorescein solution was dropped into the nasal sinuses in three different head positions, and the fluorescein deposition was evaluated. A prospective cohort study was performed to validate the results in 20 postoperative CRS patients. The cortisol level, symptom VAS and the frontal recess endoscopy scores were evaluated pre- and postoperatively. RESULTS: The frontal recess delivery of fluorescein was better in the Mygind and vertex-to-floor positions than in the head back position. The cortisol level of patients dropped markedly after taking oral methylprednisolone, but returned to baseline when replaced with budesonide drops. The pre- and postoperative symptom VAS scores did not differ significantly between the two groups. Endoscopic scores of the vertex-to-floor group were significantly better than those of the Mygind group. CONCLUSION: Both the Mygind and the vertex-to-floor head positions were optimal for delivery of topical medications to the frontal recess. When applying the steroid drops, both positions were found to be safe and associated with effective relief of symptoms. The vertex-to-floor position can better improve the endoscopic scores of frontal recess and frontal sinus.

Visible light photoredox catalyzed deprotection of 1,3-oxathiolanes.

An efficient visible light photoredox catalyzed aerobic deprotection of 1,3-oxathiolanes using organic dye Eosin Y as a photocatalyst is disclosed. The deprotection procedure features the use of a metal-free catalyst, mild conditions, a broad range of substrate scope, and good functional group tolerance. 35 examples were tested under the standard conditions and most of them afforded the deprotected products in modest to high yields.

Salivary Immunoglobulin A, E, and G4 Levels Specific to Dermatophagoides pteronyssinus in Allergic Rhinitis Patients Treated With Subcutaneous Immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (AIT) is an effective treatment for allergic rhinitis (AR). During the course of AIT, many biomarkers in body fluids change. It is necessary to find effective indicators of AIT. OBJECTIVE: To examine levels of salivary immunoglobulin A, E, and G4 (IgA, IgE, and IgG4, respectively) specific to Dermatophagoides pteronyssinus (Dp-IgA, Dp-IgE, and Dp-IgG4, respectively) and their changes in AR patients undergoing subcutaneous immunotherapy (SCIT). METHODS: This study included 82 patients with AR sensitized only to Dp and 14 healthy controls. Among patients with AR, 30 patients were not treated with specific immunotherapy (group A), while the remainder (n = 52) received house dust mite SCIT in the up-dosing phase (n = 27; group B) or the maintenance treatment phase (n = 25; group C). Dp-IgA, Dp-IgE, and Dp-IgG4 levels in the saliva were measured using the enzyme-linked immunosorbent assay. Clinical symptoms, concomitant medication, and the Rhinoconjunctivitis Quality of Life Questionnaire score were recorded and correlated with immunoglobulin levels. RESULTS: Salivary Dp-IgG4 and Dp-IgA levels were significantly lower in AR patients than in healthy controls ( P < .001 for both), while Dp-IgE levels were significantly higher ( P < .001). SCIT resulted in sustained increases in Dp-IgG4 and Dp-IgA in the maintenance phase compared to the up-dosing phase ( P < .001 for both), whereas Dp-IgE only increased in the up-dosing phase ( P = .004, P < .0125). There was no correlation between the different salivary immunoglobulins and clinical scores during SCIT. CONCLUSIONS: This study shows that allergen-specific IgE levels are increased in the saliva of sensitized patients, suggesting that measuring salivary IgE testing should be further considered for the diagnosis of AR. Moreover, allergen-specific IgA and IgG4 in the saliva, which may play protective roles against allergy, may serve as objective indicators for evaluating treatment response to SCIT. However, none of the immunoglobulin reflects subjective symptoms.

Nasal septum suture combined with inferior turbinate coblation after septoplasty: Does it improve quality of life and reduce complications?

OBJECTIVE: Nasal packing is routinely applied after septoplasty. Patients, however, report feeling very uncomfortable while the packing is in place. The aim of this study was to compare the effects of nasal septum suture combined with inferior turbinate coblation to the effects of nasal packing after septoplasty. METHODS: In this study, 135 patients undergoing septoplasty were divided into 3 groups: group 1 patients had microdebrider with packing, group 2 received coblation with packing and group 3 had coblation with suture. Early postoperative quality of life and complications were compared between the 3 groups. RESULTS: The patients in group 1 experienced the most postoperative nasal pain, headache, dysphagia, sleep disturbance and bleeding on the night of surgery; while the patients in group 3 experienced the fewest symptoms. No difference in epiphora was observed between the 3 groups. More pain and bleeding were experienced when comparing the pack removal (Group 1 and 2) with the clearance of the nasal cavity (Group 3). We noted one case of postoperative bleeding in group 1, one septal hematoma in group 1 and a second septal hematoma in group 2. No such postoperative complications were found in group 3. CONCLUSION: Nasal septum suture combined with inferior turbinate coblation was not only associated with less pain, increased patient satisfaction and an improved quality of life; but also reduced postoperative complications. Our results confirm that it is a more comfortable, reliable alternative to the more common nasal packing.