OBJECTIVE:Traumatic brain injury (TBI) leads to immune dysregulation, which predisposes patients to infections. We hypothesized that TBI leads to poor lung bacterial clearance, due at least in part to dysfunctional neutrophil (PMN) responses. In this study, we characterized both murine and porcine models of TBI plus lung bacterial inoculation to evaluate the effects of TBI on bacterial clearance, and tested the effects of plasma harvested from human TBI patients on PMN function. DESIGN:C57BL6 mice or Yucatan mini swine underwent sham (anesthesia only) or a mild TBI using standardized methods. Four hours later, mice were inoculated with Staphylococcus aureus. Pigs were inoculated with Actinobacter pleuropneumoniae immediately after TBI. At prespecified timepoints after inoculation (24 hr for mice and 72 hr for pigs), animals were euthanized and bronchoalveolar lavage (BAL) and blood were collected, and lung was harvested for further analyses. Plasma from TBI patients was used to perform in vitro assessment of PMN function. SUBJECTS:C57BL6 mice, Yucatan mini swine, healthy volunteers, and TBI patients. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:In both animal models, TBI predisposed to poor pulmonary bacterial clearance despite significantly increased PMNs in BAL and blood. In vitro, treatment of PMNs with plasma or plasma-derived extracellular vesicles (EVs) from TBI patients led to increased nondirectional chemokinesis, less reactive oxygen species production, and decreased ability to phagocytose. CONCLUSIONS:TBI leads to decreased bacterial clearance in the lung in models of TBI + bacterial lung infection, despite increased PMN counts in lung and blood. This is secondary to inappropriate PMN function after TBI, which we demonstrated in vitro via multiple functional assays to be caused, in part, by systemic factors in the plasma, including EVs. Further studies are required to understand the link between TBI and PMN dysfunction that leads to increased susceptibility to bacterial lung infection.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that various of the flow cytometry plots featured in Fig. 6A subsequently appeared in six papers written by different authors at different research institutes that were published in the years 2017‑8, one of which has since been retracted (a paper in Oncology Research). Furthermore, the possible duplication of a western band for the Msi‑1 experiments shown in Fig. 7B was also noted on p. 643, where the same data were apparently used to present two different experimental conditions. The authors were contacted by the Editorial Office to offer an explanation for the issues described above, and they have replied to say that, since this article is old, the digitized raw data for this paper were discarded in accordance with the institute's data retention policy after the mandated retention period; moreover, the authors maintain full confidence in the validity and reproducibility of their overall findings. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, however, we are issuing an Expression of Concern to notify readers of this potential problem. [International Journal of Molecular Medicine 35: 637‑644, 2015; DOI: 10.3892/ijmm.2015.2075].

PURPOSE:Hearing loss is a major global health challenge, and pure-tone audiometry remains the gold standard for assessing auditory thresholds. However, conventional clinical audiometry requires specialized sound-proof booths, which limit its accessibility in resource-constrained settings. To address this limitation, we developed and evaluated a portable audiometry system, designated as the E200, incorporating active noise control (ANC) technology with integrated supra-aural earphones. METHODS:In this 2-phase study, reference equivalent threshold sound pressure level calibration was first performed on 183 volunteers comparing E200 to conventional clinical pure-tone audiometric testing. Subsequently, we prospectively enrolled 114 participants with diverse otologic pathologies from tertiary otology clinics to evaluate the validity of the E200 audiometric system. RESULTS:Data from 228 ears were collected from 114 participants, with 7 frequencies tested/ear, resulting in 1596 sets of data. The two one-sided test equivalence analysis demonstrated that all tested frequencies met the equivalence criterion at the ±5 dB margin. Pure-tone average (PTA) was derived from the arithmetic mean of air-conduction thresholds at standard speech frequencies (0.5, 1, 2, and 4 kHz), with hearing loss severity classified according to WHO (2021) criteria: normal (<20 dB hearing level [HL]), mild-to-moderate (20-<50 dB HL), and moderate-to-severe (≥50 dB HL). Both Bland-Altman plots and Cohen's κ statistics demonstrated good agreement with the PTA results. CONCLUSIONS:This ANC-integrated portable audiometer demonstrates promising potential for hearing screening outside conventional sound-proof booths; however, its long-term clinical value and practical applications require further investigation and validation.

Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer's disease and chronic traumatic encephalopathy. Preclinical models are essential for exploring how mild TBI leads to neuronal dysfunction and neurodegeneration. Using a mouse model, we applied repetitive, mild, side-alternating impacts to induce rapid head rotational acceleration-deceleration. A novel odor-based learning and memory task was developed to address TBI-related vision impairments. Our findings revealed that this side-impact model specifically affects the hippocampus, evidenced by activated CD68+ microglia appearing in the dentate gyrus, stratum lacunosum-moleculare, and corpus callosum. Importantly, no olfactory dysfunction was observed. However, injured mice exhibited learning and memory deficits in an olfaction-based task. These results suggest that repetitive mild TBI damages hippocampal regions, leading to cognitive dysfunction characterized by impaired learning and memory, as demonstrated by this novel behavioral method.

Most patients with sensorineural hearing loss (SNHL) may initially experience high-frequency hearing loss linked to greater vulnerability of outer hair cells (OHCs) in the cochlear basal turn. However, the molecular mechanism underlying this susceptibility in the high-frequency region remains unclear. Here, NOX2 is first identified as a differentially expressed gene related to oxidative damage in the apical and basal turns through single-cell RNA sequencing. In mouse cochleae damaged by neomycin and noise, Nox2-positive OHCs increase progressively from the apex to base, indicating that NOX2 expression clearly differed significantly between the apical and basal OHCs. In NOX2 knockout mice, OHC damage caused by neomycin and noise exposure is significantly reduced. Furthermore, knocking out NOX2 increases the expression of Nrf2 in the cytoplasm and Nrf2 nuclear translocation in OHCs. In addition, Nrf2 inhibitors counteract the protective effect of NOX2 knockout against neomycin. Finally, when Nox2 is used as the target, ginsenoside Rg1 is identified as a compound with protective effects against neomycin-induced hearing loss. In summary, these results indicate NOX2 is highly correlated with high-frequency OHCs vulnerability in the cochlea and is a potential intervention target for the clinical treatment of SNHL.

Impairment in visual function is common after traumatic brain injury (TBI) in the clinical setting, a phenomenon that translates to pre-clinical animal models as well. In Morris et al. (2021), we reported histological changes following weight-drop-induced TBI in a rodent model including retinal ganglion cell (RGC) loss, decreased electroretinogram (ERG) evoked potential, optic nerve diameter reduction, induced inflammation and gliosis, and loss of myelin accompanied by markedly impaired visual acuity. In this review, we will describe several pre-clinical TBI models that result in injuries to the visual system, indicating that visual function may be impaired following brain injury induced by a number of different injury modalities. This underscores the importance of understanding the role of the visual system and the potential detrimental sequelae to this sensory modality post-TBI. Given that most commonly employed behavioral tests such as the Elevated Plus Maze and Morris Water Maze rely on an intact visual system, interpretation of functional deficits in diffuse models may be confounded by off- target effects on the visual system.

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker's organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker's organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Repetitive mild traumatic brain injury (rmTBI, e.g., sports concussions) may be associated with both acute and chronic symptoms and neurological changes. Despite the common occurrence of these injuries, therapeutic strategies are limited. One potentially promising approach is N-methyl-D-aspartate receptor (NMDAR) blockade to alleviate the effects of post-injury glutamatergic excitotoxicity. Initial pre-clinical work using the NMDAR antagonist, memantine, suggests that immediate treatment following rmTBI improves a variety of acute outcomes. It remains unclear (1) whether acute memantine treatment has long-term benefits and (2) whether delayed treatment following rmTBI is beneficial, which are both clinically relevant concerns. To test this, animals were subjected to rmTBI via a weight drop model with rotational acceleration (five hits in 5 days) and randomized to memantine treatment immediately, 3 months, or 6 months post-injury, with a treatment duration of one month. Behavioral outcomes were assessed at 1, 4, and 7 months post-injury. Neuropathological outcomes were characterized at 7 months post-injury. We observed chronic changes in behavior (anxiety-like behavior, motor coordination, spatial learning, and memory), as well as neuroinflammation (microglia, astrocytes) and tau phosphorylation (T231). Memantine treatment, either immediately or 6 months post-injury, appears to confer greater rescue of neuroinflammatory changes (microglia) than vehicle or treatment at the 3-month time point. Although memantine is already being prescribed chronically to address persistent symptoms associated with rmTBI, this study represents the first evidence of which we are aware to suggest a small but durable effect of memantine treatment in mild, concussive injuries. This effect suggests that memantine, although potentially beneficial, is insufficient to treat all aspects of rmTBI alone and should be combined with other therapeutic agents in a multi-therapy approach, with attention given to the timing of treatment.

Abstract Background: Noise-induced hearing impairment can mediate delayed injury of spiral neurons (SGNs), resulting in degeneration of nerve fibers, synaptic degeneration and even death of SGNs. We believe that delayed injury is related to mitochondrial energy metabolism disorders. Results: We investigated ATP and the electron transport chain (ETC) in rat SGNs after noise injury and found that with prolonged injury time, ATP synthesis and the expression of complexes II and IV decreased, indicating the functional decline of the ETC. The maintenance of ETC function is related to subunit import and assembly of the complex. The disulfide relay mechanism controlled by the apoptosis inducing factor/coiled-coil-helix-coiled-coil-helix domain-containing protein 4（AIF/CHCHD4) pathway can regulate mitochondrial protein import. The results showed that AIF expression in SGNs decreased after noise exposure, indicating that noise damage to SGNs can restoreintramitochondrial protein input by downregulating the AIF/CHCHD4 pathway, hinderingETC function. Conclusion: After noise injury, the mitochondrial function markers, ATP and complexes II/IV down-expressed , indicating insufficiency of ECT function leaded to delay injured SGNs. And the down-regulation of AIF/CHCHD4 function was a possible mechanism that hindered ECT function.

Wen, Liting MMed*; Zhang, Yukai MMed*; Chen, Jun MD; Qiu, Jianhua MD Author Information

There still is inadequate literature regarding the surgical indications and postoperative outcomes of cochlear implantation (CI) in patients with Branchio-oto-renal syndrome; therefore, the aim of this study was to investigate whether CI surgery improved the hearing and speech performance of children with BOR syndrome-related severe hearing loss. Clinical manifestations, genetic results,audiological features, intraoperative findings and post-CI outcomes of four children were ascertained and analysed. All patients had bilateral profound HI before CI). The surgery of one patient with aural atresia and complex ear deformity was rather challenging, but the outcome after CI was satisfactory. However,auditory and speech performance of other three patients wasn’t good enough, which was probably related to cochlear nerve deficiency.

中耳手术中通常会使用某种填塞材料以达到支撑、止血、吸水、防止粘连和促进愈合等作用.由于中耳粘膜对异物非常敏感[1],填塞物可能会引起炎症反应、异物反应、鼓室粘连、纤维化及新骨形成等[2],甚至会造成听力损伤[3],影响手术效果.理想的中耳填塞材料应该具有以下功能和特点:可为移植物提供足够的支撑;具有良好止血和吸水作用;可促进伤口愈合;可预防鼓室粘连和粘膜纤维化;生物相容性好;可降解吸收;安全性高,无毒性;具有可塑性;性价比高,材料易获得等[4];但是目前尚无完全符合上述要求的理想材料.从使用之初至今,中耳止血填塞材料经历了从不可吸收材料到可吸收材料的发展,每种材料各有利弊,但对于选择哪一种填塞材料更合适尚无统一标准.虽然也有研究者在进行中耳手术时不进行鼓室填塞,发现可以改善术后早期听力,提高患者舒适度[4],但由于手术操作难度较大,适应症少,移植物存在内陷、移位的风险,临床上很难广泛开展,故术中使用填塞材料仍然不可或缺.本文就不同类型中耳填塞材料的特性、优缺点进行综述,为其临床应用提供参考.

Objective:To explore the perioperative period characteristics of paediatric cochlear implant recipients of CHARGE syndrome with complex deformities. Methods:Retrospective case series of CHARGE syndrome were included. Radiological results, intraoperative findings, surgical planning and post-operative complications were analyzed. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre and post-operatively to measure auditory speech rehabilitation outcomes. Results:Five prelingual profoundly deaf children were identified, aged from 14 months to 60 months. All patients had congenital heart disease and underwent surgery before cochlear implantation. Upper airway abnormalities were detected as choanal atresia, laryngomalacia and tracheal stenosis. All ten ears showed cochlear abnormalities（Incomplete partition Ⅱ）, eight of them combined with secretory otitis media and/or middle ear deformity. All patients underwent single side surgery using standard transmastoid facial recess approach. Full insertion of the electrode was achieved in two cochleas, while partial insertion was done in three cochleas. Three ears with absent auditory nerves in MRI showed no response in the neural remote test. All patients had improved audio-speech performance with CAP scores 3.0±0.7 and 3.6±0.9, SIR scores 1.2±0.4 and 1.8±0.8, IT-MAIS scores 18.8±9.1 and 26.2±10.0, MUSS scores 2.2±2.4 and 7.2±8.3 after twelve months and twenty-four months follow up. Conclusion:Cochlear implantation in patients with CHARGE syndrome is a challenge in both its surgical and rehabilitation aspects due to multiple abnormalities. Adequate treatment planning is necessary for safe and effective surgery, including airway structures and intricate temporal bone landmarks.

目的 探讨语前聋患儿双模式(一侧人工耳蜗植入,对侧配戴助听器)干预与双侧人工耳蜗植入(co-chlear implantation,CI)后早期听觉言语康复效果以及生活质量,为语前聋患儿双侧干预模式的选择提供参考.方法 回顾性分析2016～2019年行双侧CI 28例(双侧CI组)和双模式干预28例(双模式组)语前聋患儿的临床资料,双侧CI组的平均植入年龄和术前助听器使用时长低于双模式组.所有患儿均于开机时、开机1、3、6和12个月时完成听觉行为分级标准(CAP)、婴幼儿有意义听觉整合量表(IT-MAIS)、言语可懂度分级标准(SIR)、有意义使用言语量表(MUSS)问卷填写,并于术后2±0.76年完成中文版CI儿童家长观点调查问卷(MPP),比较两组结果.结果 双模式组IT-MAIS得分在开机时(F=16.52,P<0.001)、开机1个月(F=12.02,P=0.001)、开机3个月(F=4.27,P=0.043)高于双侧CI组,之后两组间IT-MAIS得分无统计学差异(P>0.05).双模式组CAP分级在开机时(F=9.50,P=0.003)、开机1个月(F=8.70,P=0.005)高于双侧CI组,随后两组间CAP分级无统计学差异(P>0.05).双模式组术后MUSS得分高于双侧CI组(F=5.46,P=0.023).在开机时、开机1个月两组间SIR分级无统计学差异(P>0.05),在开机3个月(F=4.50,P=0.039)、6个月(F=10.89,P=0.002)和12个月时(F=5.46,P=0.023)双模式组SIR分级高于双侧CI组.MPP问卷的幸福感(F=9.15,P=0.004)、社会关系(F=5.03,P=0.029)和教育(F=7.97,P=0.007)维度得分双模式组高于双侧CI组,在交流、基本功能、自立能力、CI的效果和影响以及对患儿的支持维度两组间得分无统计学差异(P>0.05).结论 双侧CI与双模式干预患儿术后听觉言语能力均能取得较大进步;尽管术后早期双模式干预患儿的听觉言语能力进步更明显,但考虑到植入年龄、术前助听器使用时间等因素的影响,尚不能认为双模式干预的效果优于双侧CI.

目的 探讨儿童慢性化脓性中耳炎行鼓室成形术的疗效.方法 回顾性分析51例(51耳)行鼓室成形术的慢性化脓性中耳炎儿童年龄、手术方法、鼓膜愈合率、术后听力疗效.结果 51例患儿年龄7～17岁,平均12.98±3岁,51耳的鼓膜愈合率为90.2％(46/51);将患者分为≤13岁(26例)及>13岁(25例)两组,鼓膜愈合率分别为88.46％(23/26)、92.0％(23/25),差异无统计学意义(P>0.05);完成Ⅰ型鼓室成形术者35耳(68.63％),Ⅱ型鼓室成形术者16耳(31.37％),Ⅰ型和Ⅱ型鼓室成形术者术后术耳气骨导差较术前均有显著缩小(P<0.05);听力改善总有效率为78.43％(40/51),Ⅰ型和Ⅱ型鼓室成形术者听力改善的有效率分别为80％(28/35),75％(12/16).结论 7岁以上慢性化脓性中耳炎儿童的年龄可能不是影响鼓室成形术成功率的关键因素,但手术仍需谨慎.

目的 探究Waardenburg综合征患儿人工耳蜗植入后听觉言语康复效果以及生活质量情况,分析听觉言语康复效果影响因素,为Waardenburg综合征人工耳蜗植入患儿的术后效果评价提供参考.方法 回顾2011-2019年在我科行人工耳蜗植入的Waardenburg综合征(WS)患儿以及对照组患儿临床资料.随访汇总两组患儿的听觉行为分级标准(CAP)得分、言语可懂度分级标准(SIR)得分和中文版CI儿童家长观点调查问卷(MPP)得分,评估WS患儿人工耳蜗植入术后听觉言语康复效果和个人生活质量情况,并分析术后听力言语康复效果的影响因素.结果 WS组术后CAP分级和SIR分级无统计学差异.两组患儿术后生活质量得分,对照组患儿在交流(F=10.60,P=0.002)、幸福感(F=7.06,P=0.010)和社会关系(F=6.99,P=0.011)维度得分高于WS组.植入年龄(Z=-2.123,P=0.034)、监护人文化水平(Z=-2.106,P=0.035)、使用耳蜗时间(Z=-3.184,P=0.001)是WS患儿人工耳蜗术后CAP分级的影响因素.植入年龄(Z=-2.273,P=0.023)、监护人文化水平(Z=-2.026,P=0.039)、使用耳蜗时间(Z=-2.922,P=0.003)是WS患儿人工耳蜗术后SIR分级的影响因素.结论 WS患儿人工耳蜗术后听觉言语康复效果良好,植入年龄、监护人文化水平、使用耳蜗时间与听觉言语康复水平相关.尽管生活质量与非综合征性感音神经性聋患儿有差异,但具体原因还需要进一步排除混杂因素研究和探索.