Ischemia-reperfusion (I/R) injury, uncommon among patients suffering from myocardial infarction, stroke, or acute kidney injury, can result in cell death and organ dysfunction. Previous studies have shown that different types of cell death, including apoptosis, necrosis, and autophagy, can occur during I/R injury. Pyroptosis, which is characterized by cell membrane pore formation, pro-inflammatory cytokine release, and cell burst, and which differentiates itself from apoptosis and necroptosis, has been found to be closely related to I/R injury. Therefore, targeting the signaling pathways and key regulators of pyroptosis may be favorable for the treatment of I/R injury, which is far from adequate at present. This review summarizes the current status of pyroptosis and its connection to I/R in different organs, as well as potential treatment strategies targeting it to combat I/R injury.

Patients with profound bilateral deafness (BD) are prone to suffering from tinnitus, which further leads to psychological comorbidities and makes it more difficult for patients to communicate with people. This study was aimed at investigating the effect of cochlear implants (CIs) on tinnitus distress and psychological comorbidities in patients with profound BD. This multicenter retrospective study reviewed 51 patients with severe postlingual BD who underwent cochlear implantation; 49 patients underwent unilateral cochlear implantation, and 2 patients underwent bilateral cochlear implantation. The patients were asked to complete all the questionnaires, including the tinnitus handicap inventory (THI), the visual analog scale (VAS) score, the Hospital Anxiety and Depression Scale Questionnaire (HADS), the Categories of Auditory Performance (CAP), and the Speech Intelligibility Rating (SIR), at least 4 months after implantation when the CI was on or off, in approximately May-June 2019. In our study, 94% (48/51) of BD patients suffered from tinnitus before CI, and 77% (37/48) of them suffered from bilateral tinnitus. In addition, 50.9% (26/51) of the CI patients were suffering from anxiety, 52.9% (27/51) of them were suffering from depression ( ), and 66.7% (34/51) (27/51) of them were suffering from anxiety or depression. Cochlear implantation could reduce tinnitus more obviously when the CI was on than when the CI was off. Cochlear implantation also reduced anxiety/depression severity. There were significantly positive correlations between tinnitus severity and anxiety/depression severity before and after surgery. Moreover, hearing improvement is positively correlated with reduction level of tinnitus, the better hearing, and the lesser severity of tinnitus. Thus, along with effective restoration of deafferentation, cochlear implantation shows positive therapeutic effects on tinnitus and psychological comorbidities, providing a reference for future clinical and research work.

Original Article Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma Hui-Ying Huang, Ke-Nan Li, Hui-Ching Lau, Chi-Yao Hsueh, Ning Cong, Ming Zhang

We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.