Psychological Distress and Meniere's Disease: A Bidirectional Two-Sample Mendelian Randomization Study.

OBJECTIVE: This study is aim to explore the causal relationship between anxiety, depression, neuroticism, and Meniere's disease (MD). STUDY DESIGN: Two-sample bidirectional Mendelian randomization (MR) analyses. SETTING: IEU, FinnGen, CTG, and UKB databases. METHODS: The genome-wide association studies data for anxiety, depression, neuroticism, and MD involved over 357,957 participants. MR was performed to explore relationships between anxiety, depression, neuroticism, and MD. Sensitivity analyses were performed to assess the robustness of the MR results. Reverse MR was used to exclude the possibility of reverse causality. Finally, multivariate MR was performed to explore the collinear relationships between neuroticism subclusters. RESULTS: MR results showed that anxiety and depression are not causes of MD, nor does MD cause anxiety and depression. Elevated neuroticism sum score is a cause of anxiety, depression, and MD, but MD does not lead to an increase in the level of neuroticism sum score. Further analysis showed that the 5 subclusters of neuroticism often feel lonely, mood often goes up and down, often feel fed-up, feelings easily hurt, and sensitivity to environmental stress and adversity are causes of MD. Multivariate MR analysis results suggested that the 5 neuroticism subclusters have a collinear relationship. CONCLUSION: Anxiety and depression are not causative factors of MD, and vice versa. Elevated neuroticism levels serve as a shared causative factor for anxiety, depression, and MD. Identification and effective management of neuroticism is a potential target for preventing and treating MD.

Analysis of 3 Surgical Approaches for the Treatment of Cerebrospinal Fluid Otorrhea: A Case Series Report.

Background: This case series report aimed to present three surgical approaches used for the treatment of cerebrospinal fluid (CSF) otorrhea, providing less invasive surgical options for managing this condition. Methods: Clinical data of 26 patients with CSF otorrhea, who underwent treatment using three surgical methods between June 2012 and June 2022, were retrospectively analyzed. The study collected information on patients' basic demographic characteristics, chief complaints, location of the defect, results of otorrhea endoscopic examination, findings from skull base thin-slice computed tomography (CT) examination, and causes of CSF otorrhea. Postoperative outcomes of CSF otorrhea were followed up. Results: Among the 26 cases of CSF otorrhea, there were 13 (50%) males and 13 (50%) females who underwent treatment using the three surgical methods. The etiology of CSF otorrhea included 10 (38%) cases of spontaneous CSF otorrhea, including 2 (8%) cases of congenital inner ear deformity and 8 (31%) cases without obvious inducement. Additionally, there were 5 (19%) cases of trauma, 6 (23%) cases of cholesteatoma complications, 3 (12%) cases of postoperative complications of brain tumor, 1 (4%) case of radiotherapy, and 1 (4%) case of a malignant tumor. A total of 12 (46%) cases of CSF otorrhea were treated by local repair of the defect. Furthermore, 3 (12%) cases underwent local repair of the defect combined with sealing of the tympanic sinus entrance, while 11 (42%) cases underwent local repair of the defect combined with sealing of the eustachian tube and the external auditory canal. No recurrence of CSF otorrhea was observed during the 6-month to 10-year follow-up period after surgery. Conclusion: The three methods for CSF otorrhea, including local defect repair, local defect repair combined with sealing of the tympanic sinus entrance, and sealing of the eustachian tube and the external auditory canal, demonstrated successful outcomes in appropriately selected patients.

Cochlear Implants in Deaf Patients with Novel TMPRSS3 Gene Mutation.

Objective: To investigate the effect of cochlear implants in deaf patients with TMPRSS3 gene pathogenic variations. Methods: Variations of deafness genes were detected in 2 patients with profound hearing loss. Both received unilateral cochlear implantation. Hearing and speech abilities were evaluated and analyzed before and 3 and 6 months after surgery. The analysis included post-surgery evaluation of auditory behavior (Categories of Performance [CAP]) and Speech Intelligibility Rating (SIR). Results: In the 2 patients, 3 pathogenic single nucleotide variations (SNVs) of TMPRSS3 gene and a large deletion in 21q22.3 were detected. The CAP and SIR grades increased with the recovery time. Conclusion: Cochlear implants have a good effect in patients with TMPRSS3 gene mutation deafness. Preoperative gene testing has a certain reference significance for the prognosis in patients with the deafness gene mutation.

Genetic and clinical phenotypic analysis of carney complex with external auditory canal myxoma.

Background: Mutations in PRKAR1A gene can lead to Carney complex (CNC), and most CNC patients develop cardiac and cutaneous myxomas. In particular, cardiac myxomas are a common cause of mortality in CNC patients. Cutaneous myxomas of the external ear are extremely rare, and do not have any specific clinical features Methods: In this retrospective study, we analyzed the clinical and genetic data of the proband and his family and fifty whole blood control samples selected from the molecular genetic database of our hospital. Whole exome DNA sequencing analysis was used to detect the mutation in the peripheral blood samples. Results: The results of the clinical analysis showed the presence of spotty skin pigmentation and external auditory canal myxoma in the proband as well as in his sister and mother. Whole-exome DNA sequencing showed a novel heterozygous mutation in the PRKAR1A gene i.e., c.824_825delAG (p.Gln275Leufs*2), in the proband and his sister and mother. Conclusion: In conclusion, the family members had the same autosomal dominant PRKAR1A mutation. DNA sequencing revealed a novel c.824_825delAG in exon 9 of PRKAR1A. This pathogenic mutation has not been reported previously, and may be related to the occurrence of external auditory canal myxomas and spotty pigmentation. This study broadens the genotypic spectrum of PRKAR1A mutations in CNC.

A novel mutation of X-linked recessive deafness gene POU3F4 in a boy with congenital deafness.

Purpose: To report an interstitial deletion of Xq21.1 in chromosome X in a boy with congenital deafness. Methods: The proband underwent a thorough physical examination and a detailed audiological and temporal bone computed tomography (CT) scan. Cochlear implantation was performed on the proband, and follow-up was conducted. High throughput sequencing and copy number analysis was made of peripheral blood samples from the proband, family members, and control subjects. Results: Sensorineural hearing loss was present in the boy and temporal bone CT scan showed a bilateral incomplete partition type III anomaly (IP-III). Q21.1 (79.40-83.32 Mb) of chromosome X in the proband had a copy number deletion with a fragment size of about 3.92 Mb. Categories of auditory performance scores and SIR scores of the cochlea in this child improved after surgery. Conclusion: Through the analysis of POU3F4, a novel mutation site with potentially pathogenic significance was found.Level of Evidence: 5.

[Current status of the diagnosis and treatment of temporal bone squamous cell carcinoma].

Temporal bone squamous cell carcinoma, which is rare in the clinical setting, is the most common type of temporal bone malignancy. Its rarity makes the staging, the way of temporal bone resection, the management of parotid gland and cervical lymph node, and the application of radiotherapy and chemotherapy still controversial.There is no unanimous consensus and guideline about it to date at home and abroad.This paper reviewed the recent advance in the diagnosis and treatment of temporal bone squamous cell carcinoma in the hope of providing some help and reference for the management of the disease.

Analysis of the curative effect of a domestic ear orthosis system in the treatment of congenital auricle deformity.

OBJECTIVE: To evaluate the therapeutic effect and determinants of jingle ear orthosis in the correction of infant ear malformation and to evaluate its clinical application value. METHODS: In this retrospective study, 156 patients with 233 ears who had used the beautiful ear orthosis system in Jiangxi Province in the last 3 years were included. The patients were grouped according to age at initial correction, sex, and type of deformity, and data on duration and age of orthotic use and complications were obtained. RESULTS: We studied 156 paediatric cases with 233 ear deformities, 79 of which were single-ear deformities. In total, 77 cases had an ear shape deformity, and an implicit ear was the most common deformity. For a good therapeutic effect evaluation standard above 96.57%, the mean duration of follow-up was 1 month. The initial correction age was an important factor in the correction effect while gender had no obvious influence. The difference in the mean wearing time was not statistically significant (p = 0.233, p > 0.05). There was no statistically significant difference in the ratio of correcting effects between the 6 types of deformities that were excellent or good (p = 0.086, p > 0.05). CONCLUSIONS: Domestic auricle orthosis is an effective nonsurgical treatment for ear malformation. The correction effect is related to the initial correction age. The younger the child is, the better the treatment effect is, and the shorter the treatment time is. Complications are common in older infants. Therefore, prompt non-surgical correction performed can improve the effective rate of treatment.

Retrospective analysis of massive epistaxis and pseudoaneurysms in nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: Epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC) is a common clinical critical illness, which often leads to death of patients. This article focuses on the relationship between massive epistaxis and pseudoaneurysm after radiotherapy in patients with NPC and discusses clinically relevant treatment strategies. METHODS: A review was performed in 21 patients with massive epistaxis after radiotherapy for NPC from January 2011 to December 2019, and all of the patients were examined by computed tomography angiography (CTA). We also reviewed the English literature over the past 10 years to analyze the characteristics and related causes of pseudoaneurysms in terms of the clinical stage of NPC, course of radiotherapy, and affected artery. An analysis was performed on the methods of endovascular interventional treatment of such pseudoaneurysms. RESULTS: Among the 21 patients, 19 cases had bone destruction of the skull base; 13 cases were also found to have tumor recurrence; 15 cases were in stage III or IV of NPC; pseudoaneurysms were observed in 14 cases, of which nine cases had pseudoaneurysms in the internal carotid artery (ICA), and the rest had pseudoaneurysms in the external carotid artery (ECA). These data were consistent with the results of the literature review. Analysis with imaging revealed that the petrous ICA was the common predilection site. There were 11 out of 14 cases of pseudoaneurysms with sentinel hemorrhage in the initial phase. All 14 pseudoaneurysm patients underwent endovascular interventional therapy, but one died from hemorrhagic shock during the procedure. No rebleeding was observed among the other patients during 72 h after intravascular treatment. Nevertheless, regrettably two patients died on the 10th and 17th days after intervention. CONCLUSION: Pseudoaneurysm, which was a serious complication after radiotherapy in patients with NPC, could cause massive epistaxis with high mortality. The formation of a pseudoaneurysm was closely associated with a high carcinoma stage, re-radiotherapy, and local bone destruction and infection. Most cases had sentinel epistaxis, which was considered the bleeding characteristic. The imaging material prompted that pseudoaneurysm had a predisposition to the petrous part of the ICA, while the preferred therapy was endovascular embolization treatment.

Alterations of thyroid microbiota across different thyroid microhabitats in patients with thyroid carcinoma.

BACKGROUND: In recent years, the incidence rate of Thyroid carcinoma (TC) has been increasing worldwide. Thus, research on factors of TC carcinogenesis may promote TC prevention and decrease the incidence rate. There are several studies targeting the correlation between gut microbiota and thyroid disease. Carcinogenesis of several malignancies is influenced by microbiota. However, thyroid microbiome of TC has not been revealed. This study investigated thyroid microbiota in different TC microhabitats. METHODS: We performed 16s rRNA gene sequencing using tumor tissues and matched peritumor tissues from 30 patients with TC to characterize thyroid microbiota. RESULTS: The richness and diversity of thyroid microbiota were lower in TC tumor samples than in matched peritumor tissues. At the genus level, the core microbiota of thyroid included Sphingomonas, Comamonas, Acinetobacter, Pseudomonas, Microvirgula, and Soonwooa. The abundance of Sphingomonas and Aeromonas was significantly increased in tumor tissues, while the abundance of Comamonas, Acinetobacter, and Peptostreptococcus was significantly enhanced in peritumor tissues. The combination of Comamonas and Sphingomonas could discriminate tumor samples from peritumor samples with an area under the curve (AUC) of 0.981 (95% confidence interval [CI] 0.949-1.000). The abundance of Sphingomonas was significantly higher in N1 stage than in N0 stage. Sphingomonas could distinguish between N0 and N1 stage with an AUC of 0.964 (95% CI 0.907-1.000). CONCLUSIONS: The microbial diversity and composition were significantly different between peritumor and tumor microhabitats from patients with TC, which may eventually affect TC carcinogenesis and progression. The combination of Comamonas and Sphingomonas could serve as a powerful biomarker for discrimination between tumor and peritumor tissues. Furthermore, the higher abundance of Sphingomonas was correlated with lymph node metastasis, indicating that the abundance of Sphingomonas may indicate a poor prognosis for TC patients, and Sphingomonas may play a role in promoting TC progression.

Interactions between gastric microbiota and metabolites in gastric cancer.

The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.

Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by an NOG mutation.

BACKGROUND: The noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness. METHODS: In a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them. RESULTS: The sequencing analysis indicated that in the proband, the NOG gene had a c.532T > C, p.C178R (cytosine deletion, NM_005450.6:c.532T > C), leading to an amino acid change. The proband's father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation. CONCLUSION: Analysis of this family showed that the novel presentation of the c.532T > C, p.C178R mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.

KLF4 upregulation is involved in alternative macrophage activation during secondary Echinococcus granulosus infection.

The objective of this study was to investigate macrophage polarization during the early stages of secondary Echinococcus granulosus sensu lato (E. granulosus s.l.) infection. We observed an early initial increase in inflammatory genes (peaking at 5-10 days) and a later rise in M (IL-4)-like genes (still rising by day 15). In addition, we showed that the induction of M (IL-4)-like genes was paralleled by an increase in expression of the transcription factor KLF4. Most of the changes observed in vivo were reproduced in vitro upon the culture of normal peritoneal macrophages with live E. granulosus s.l. protoscoleces (PSC), and that knockdown of KLF4 in this system attenuates M (IL-4) differentiation. Our results suggest that KLF4 pathway contributes to the differentiation of macrophages towards M (IL-4)-like phenotype during early stages of secondary E. granulosus s.l. infection.

Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.

BACKGROUND: Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized. METHODS: Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference. Invasion potential was determined by Matrigel and three-dimensional invasion. The secretion of matrix metalloproteinase 2 (MMP2) and MMP9 were measured by ELISA. Protein levels were assessed by Western blotting and immunohistochemistry. Protein-protein interactions were determined by immunoprecipitation. An experimental mouse model was generated to investigate the gene regulation in tumor growth and metastasis. RESULTS: Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. Overexpression of NAP1 in lowly invasive NSCLC cells enhances MMP9 secretion and invasion potential, whereas NAP1 silencing in highly invasive NSCLC cells produces opposing effects in comparison. Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells. CONCLUSIONS: Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis.

Novel Bougie for the Management of Esophageal Coins in Children: An Observational Study.

OBJECTIVES: To determine the efficacy and safety of a novel bougie for the removal of esophageal coins lodged in the proximal esophagus. SUBJECTS AND METHODS: This was an observational study. Medical records were reviewed of patients who were confirmed with esophageal coins between July 2015 and October 2016 in our department. Sixty-three patients, upper esophageal coins were confirmed by radiographs, were treated by using this novel bougie to remove esophageal coins. RESULTS: A total of 63 children were enrolled in this study. Sixty coins (95%) were removed successfully. The coin was extracted on the first attempt in 56 cases (89%), the second attempt in 3 cases (5%), and the third attempt in 1 case (2%). Two coins retained in the esophagus underwent endoscopy. In the remaining patient, the coin passed into the stomach and was confirmed to be passed in the stool within 48 hours. No serious complications occurred in any subject. CONCLUSIONS: Our novel bougie procedure is likely a safe, highly efficient approach to managing esophageal coins given that no serious complications of the 63 patients were reported. This simple technique may provide another valuable option to physicians.

The transplantation of induced pluripotent stem cells into the cochleae of mature mice.

OBJECTIVE: Stem cell transplantation is an effective method for treating sensorineural hearing loss (SNHL), but its safety needs further study. This study aimed to reveal the differentiation outcome of induced pluripotent stem cells (iPSCs) after they were transplanted into cochleae. METHODS: iPSCs were labelled with CM-Dil and identified by flow cytometry. Twenty 6-8-week-old ICR mice were divided into experimental (A) and control (B) groups. Ten mice were microinjected with CM-Dil-labelled iPSC suspension (group A) or an equal volume DMEM (group B) into the left ear cochlea. The tthresholds of all mice were tested by auditory brainstem response (ABR) at 1 week pre-surgery and 4 weeks post-surgery. Differentiated cells were identified by immunohistochemical staining for neuronal cell markers (nestin, neurofilament-M), and teratoma formation was determined by HE staining. RESULTS: The ABR thresholds in groups A and B at one week pre-surgery (24.50±5.50 vs. 26.00±6.15 dB SPL) and at 4 weeks post-surgery (70.50±4.97 vs. 68.00±5.37 dB SPL) were not significantly different; however, in both groups, the thresholds were lower at pre-surgery than at 4 weeks post-surgery. In group A, CM-Dil-labelled iPSCs were observed in the cochlear perilymph, endolymph, and modiolus, and some red fluorescence-labelled cells expressed neural cell markers. In group B, no fluorescence was observed in the cochleae, but teratomas were observed in some cochleae. A teratoma was observed in each of two cochleae after iPSCs transplantation by HE staining. CONCLUSION: Mouse iPSCs can differentiate into cells with neuronal cell markers 4 weeks post-cochlear transplantation, and transplanted undifferentiated iPSCs may form teratomas. However, in the short-term, hearing loss in mice caused by cell transplantation through round window pathways cannot be improved by cochlear iPSC transplantation.

Transplantation of mouse-induced pluripotent stem cells into the cochlea for the treatment of sensorineural hearing loss.

CONCLUSION: Mouse-induced pluripotent stem cells (iPSCs) could differentiate into hair cell-like cells and spiral ganglion-like cells after transplantation into mouse cochleae, but it cannot improve the auditory brain response (ABR) thresholds in short term. OBJECTIVE: To evaluate the potential of iPSCs for use as a source of transplants for the treatment of sensorineural hearing loss (SNHL). METHODS: Establishing SNHL mice model, then injecting the iPSCs or equal volume DMEM basic medium into the cochleae, respectively. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess the survival, migration, differentiation of the transplanted iPSCs in cochleae and then recorded the ABR threshold in different time. Hematoxylin-eosin (HE) staining was used to observe the teratoma formation. RESULTS: Four weeks after transplantation, CM-Di1-labeled iPSCs could be found in the modiolus and Rosenthal's canal (RC), and some of them could expressed auditory hair cell markers or spiral ganglion neuron makers in group A, but not found in group B and C. As to the ABR threshold, no significance differences were found between pre- with postoperative in group A or B. In our study, no teratoma was observed in the cochleae.

A large psammomatoid ossifying fibroma with proptosis: A case report.

The psammomatoid ossifying fibroma (POF) is a rare and benign fibro-osseous lesion predominantly affecting the paranasal sinuses and orbits of children and young adults. The diagnosis and management of the lesion remains challenging. The present study reported a rare case of a large POF in a 39-year-old male patient. The patient had a 30 year history of a slowly growing tumor and this had resulted in right craniofacial deformity, as well as right lateral displacement of the eye ball. Due to the large tumor size, surgical removal of the lesion was the predominant treatment. At 5 months after complete surgical resection, the patient was free from any symptoms. The radiological and histological findings, as well as the surgical management, were presented and the relevant literature was reviewed.

[Advance research on the pathogenesis of middle ear cholesteatoma].

Cholesteatoma is a non-neoplastic, keratinizing lesion, characterized by the proliferation of epithelium with aberrant micro-architecture into the middle ear or mastoid cavity. The exact pathogenic molecular mechanisms behind the formation and propagation of cholesteatoma remain unclear. Without timely detection and intervention, cholesteatomas can become dangerous and result in numerous intracranial and extracranial complications. In this review, the current researches about inflammatory mediators, enzymatic activity, growth factors, oxidative stress,infection and genetics in acquired cholesteatoma pathogenesis are discussed.

[Giant ossifying fibroma of nasal cavity and nasal sinuses: one case report].

A 39 years old male patient was admitted with the right of facial abnormalities and gradually protruding in right eye more than 30 years. CT shows high mixed density, clear boundary, and the right eye was crowded to the right. Giant tumor had completely been excised, and the result was fine. The outline figure and function of patients were obviously improved. The pathological examination after resection showed ossifying fibroma.