Hearing loss prevalence and burden of disease in China: Findings from provincial-level analysis.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS: The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.

Functional prediction of the potential NGLY1 mutations associated with rare disease CDG.

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

Characterization and Molecular Mechanism of Aminoglycoside-6-Adenyl Transferase Associated with Aminoglycoside Resistance from Elizabethkingia meningoseptica.

Purpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene (ant(6)FMS-007) was predicted. This study aimed to characterize the biochemical function of ANT(6)FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes. Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015-2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6)FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites. Results: The predictive ANT(6)FMS-007 protein could inactivate STR by modifying STR with ATP to form STR-AMP. Four active sites (Asp-38, Asp-42, Lys-95, and Lys-213) of ANT(6)FMS-007 were identified. Thirty-one EM clinical isolates (74%) carried the ant(6) gene. Eight EM clinical isolates containing the ant(6) gene had MIC values (<=32µg/mL) lower by at least 16-fold than FMS-007 (512µg/mL) for STR, and N59H and K204Q were the common mutations in the ant(6) gene. Conclusion: This assay verified the biochemical function of the predictive gene ant(6)FMS-007 and could provide an alternative method to study resistant gene function in multi-drug-resistant bacteria. The inconsistency between genotype and phenotype of resistant genes indicated that the combination of resistance gene detection and functional analysis could better provide precision medicine for clinical use.

Cross-Modal Contrastive Hashing Retrieval for Infrared Video and EEG.

It is essential to estimate the sleep quality and diagnose the clinical stages in time and at home, because they are closely related to and important causes of chronic diseases and daily life dysfunctions. However, the existing "gold-standard" sensing machine for diagnosis (Polysomnography (PSG) with Electroencephalogram (EEG) measurements) is almost infeasible to deploy at home in a "ubiquitous" manner. In addition, it is costly to train clinicians for the diagnosis of sleep conditions. In this paper, we proposed a novel technical and systematic attempt to tackle the previous barriers: first, we proposed to monitor and sense the sleep conditions using the infrared (IR) camera videos synchronized with the EEG signal; second, we proposed a novel cross-modal retrieval system termed as Cross-modal Contrastive Hashing Retrieval (CCHR) to build the relationship between EEG and IR videos, retrieving the most relevant EEG signal given an infrared video. Specifically, the CCHR is novel in the following two perspectives. Firstly, to eliminate the large cross-modal semantic gap between EEG and IR data, we designed a novel joint cross-modal representation learning strategy using a memory-enhanced hard-negative mining design under the framework of contrastive learning. Secondly, as the sleep monitoring data are large-scale (8 h long for each subject), a novel contrastive hashing module is proposed to transform the joint cross-modal features to the discriminative binary hash codes, enabling the efficient storage and inference. Extensive experiments on our collected cross-modal sleep condition dataset validated that the proposed CCHR achieves superior performances compared with existing cross-modal hashing methods.

Paper-Based Humidity Sensor for Respiratory Monitoring.

Flexible respiratory monitoring devices have become available for outside-hospital application scenarios attributable to their improved system wearability. However, the complex fabrication process of such flexible devices results in high prices, limiting their applications in real-life scenarios. This study proposes a flexible, low-cost, and easy-processing paper-based humidity sensor for sleep respiratory monitoring. A paper humidity sensing model was established and sensors under different design parameters were processed and tested, achieving high sensitivity of 5.45 kΩ/%RH and good repeatability with a matching rate of over 85.7%. Furthermore, the sensor patch with a dual-channel 3D structure was designed to distinguish between oral and nasal breathing from origin signals proved in the simulated breathing signal monitoring test. The sensor patch was applied in the sleep respiratory monitoring of a healthy volunteer and an obstruct sleep apnea patient, demonstrating its ability to distinguish between different respiratory patterns as well as various breathing modes.

Single Cell Raman Spectroscopy Deuterium Isotope Probing for Rapid Antimicrobial Susceptibility Test of Elizabethkingia spp.

Nosocomial infection by multi-drug resistance Elizabethkingia spp. is an emerging concern with severe clinical consequences, particularly in immunocompromised individuals and infants. Efficient control of this infection requires quick and reliable methods to determine the appropriate drugs for treatment. In this study, a total of 31 Elizabethkingia spp., including two standard strains (ATCC 13253 and FMS-007) and 29 clinical isolates obtained from hospitals in China were subjected to single cell Raman spectroscopy analysis coupled with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could determine antimicrobial susceptibility of Elizabethkingia spp. in 4 h, only one third of the time required by standard broth microdilution method. The method could be integrated into current clinical protocol for sepsis and halve the report time. The study also confirmed that minocycline and levofloxacin are the first-line antimicrobials for Elizabethkingia spp. infection.

Image-guided cochlear access by non-invasive registration: a cadaveric feasibility study.

Image-guided cochlear implant surgery is expected to reduce volume of mastoidectomy, accelerate recovery, and improve safety. The purpose of this study was to investigate the safety and effectiveness of image-guided cochlear implant surgery by a non-invasive registration method, in a cadaveric study. We developed a visual positioning frame that can utilize the maxillary dentition as a registration tool and completed the tunnels experiment on 5 cadaver specimens (8 cases in total). The accuracy of the entry point and the target point were 0.471 ± 0.276 mm and 0.671 ± 0.268 mm, respectively. The shortest distance from the margin of the tunnel to the facial nerve and the ossicular chain were 0.790 ± 0.709 mm and 1.960 ± 0.630 mm, respectively. All facial nerves, tympanic membranes, and ossicular chains were completely preserved. Using this approach, high accuracy was achieved in this preliminary study, suggesting that the non-invasive registration method can meet the accuracy requirements for cochlear implant surgery. Based on the above accuracy, we speculate that our method can also be applied to neurosurgery, orbitofacial surgery, lateral skull base surgery, and anterior skull base surgery with satisfactory accuracy.

Minimally Invasive Cochlear Implantation Assisted by Bi-planar Device: An Exploratory Feasibility Study in vitro.

BACKGROUND: A single drilled tunnel from the lateral mastoid cortex to the cochlea via the facial recess is essential for minimally invasive cochlear implant surgery. This study aimed to explore the safety profile of this kind of new image-guided and bi-planar device-assisted surgery procedure in vitro. METHODS: Image-guided minimally invasive cochlear implantations were performed on eight cadaveric temporal bone specimens. The main procedures were: (1) temporal bone specimens were prepared for surgery and fiducial markers were registered. (2) computed tomography (CT) scans were performed for future reference. (3) CT scan images were processed and drill path was planned to minimize cochlear damage. (4) bi-planar device-assisted drilling was performed on the specimens using the registration. (5) surgical safety was evaluated by calculating the deviation between the drill and the planned paths, and by measuring the closest distance between the drilled path and critical anatomic structures. RESULTS: Eight cases were operated successfully to the basal turn of the cochlear with intact facial nerves (FNs). The deviations from target points and entrance points were 0.86 mm (0.68-1.00 mm) and 0.44 mm (0.30-0.96 mm), respectively. The angular error between the planned and the drilled trajectory was 1.74° (1.26-2.41°). The mean distance from the edge of the drilled path to the FN and to the external canal was 0.60 mm (0.35-0.83 mm) and 1.60 mm (1.30-2.05 mm), respectively. In five specimens, the chorda tympani nerves were well preserved. In all cases, no injury happened to auditory ossicles. CONCLUSIONS: This exploratory study demonstrated the safety of the newly developed image-guided minimally invasive cochlear implantation assisted by the bi-planar device and established the operational procedures. Further, more in vitro experiments are needed to improve the system operation and its safety.

[Clinical analysis of tympanosclerosis: characteristics and treatment].

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical management of tympanosclerosis. METHOD: The data of 73 patients who underwent surgery for tympanosclerosis were retrospectively analyzed with respects to the clinical characteristics, diagnosis and management. RESULT: Seventy-three patients with tympanosclerosis (involving 73 ears) , including 17 patients with sclerosis of tympanic membrane (type I), 23 patients with fixed Malleus-incus complex (type II), 8 (type III) with fixed stapes, and 25 (type IV) with extensive typannosclerosis. Sclerosis was seen most frequently in the malleus, incus and attic, followed by the tympanic membrane, incudomalleolar joint and other regions. Audiometry was performed for all the patients 1 weeks before and 1 year( the least) after operation, which were (51.70 ± 14.93)dB HL and (36.24 ± 11.58) dB HL respectively, with success rate 83% (61/73). CONCLUSION: Most of the patients suffer from conductive hearing loss. Teatment of the sclerosis around stapes is a key point. Acording to the sites of lesion and hearing level, hearing structures should be reconstructed by the rules of tympanoplasty and stapes surgery.

[Clinical analysis of petrous bone cholesteatoma: characteristics, diagnosis and treatment].

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical management of petrous bone cholesteatoma. METHOD: The data of 12 patients who underwent surgery for petrous bone cholesteatoma(PBC) were retrospectively analyzed with respects to the clinical characteristics, diagnosis and management. RESULT: Seven cases were characterized by a long otitis media history, severe hearing loss, and facial paralysis. In contrast, 5 cases were characterized with the symptoms of facial paralysis, hearing loss and vertigo attack and the absence of early otorrhea history. Trans labyrinth approach was chosen for 2 cases,while trans labyrinth-cochlear approach for 10. Cochlea was involved in 10 cases, while internal auditory canal in 9 and semicircular canal in 11. Otoscope was used in 1 case. Four patients were treated by partial resection of petrous apex and ear canal closure with good results. After years of follow-up, three recurrence cases were operated for a second time. Simultaneous facial nerve anastomosis or decompression was performed. The function of facial nerve recovered from V-VI to Ill-IV (House and Brackmann grading) in 6 anastomosis cases and from IV-V to II- IlI in 3 cases of decompression. CONCLUSION: Petrous bone cholesteatoma was characterized by severe hearing loss, and facial paralysis. Surgical approaches are decided according to the extent of lesion and hearing status. Our study indicated that otoscope would help to ensure a radical removal of the pathology in cases with deep involvement and restricted vision. Partial resection of petrous bone and ear canal closure could be effective solution for challenging cerebrospinal fluid otorrhea with large dural defects and protecting vital neurovascular structures.

[Analysis of misdiagnosis and differential diagnosis of infectious mononucleosis in adults].

OBJECTIVE: To explore the clinical characteristics of infectious mononucleosis (IM) in adults. METHOD: Medical records of 50 adult IM patients admitted in hospital were analyzed retrospectively. RESULT: Diagnosis delayed group contained 16 patients (32% of total patients) and was significantly different from the diagnosis in-time group in typical symptoms, signs and laboratory findings of IM. CONCLUSION: The clinical manifestations of adult IM are rather complicated and nonspecific to diagnosis. History collection and physical examination in detail are helpful for early diagnosis.