Encapsulation of Platinum Prodrugs into PC7A Polymeric Nanoparticles Combined with Immune Checkpoint Inhibitors for Therapeutically Enhanced Multimodal Chemotherapy and Immunotherapy by Activation of the STING Pathway.

Tumor immunotherapy has emerged as one of the most promising therapeutic methods to treat cancer. Despite its clinical application, the immunosuppressive tumor microenvironment compromises the therapeutic efficiency of this technique. To overcome this limitation, many research efforts have been devoted to the development of agents that reprogram the immunosuppressive tumor microenvironment through novel mechanisms. Over the last decade, compounds that intervene through the immunogenic stimulator of interferon genes (STING) pathway have emerged with potential for clinical development. Herein, the encapsulation of chemotherapeutic platinum complexes with a polymer with a cyclic seven-membered ring (PC7A)-based polymer into pH-responsive nanoparticles for multimodal therapeutically enhanced chemotherapy and immunotherapy is presented. This study represents the first nanomaterial with a dual activation mechanism of the STING pathway through DNA fragmentation as well as PC7A binding. The combination of these nanoparticles with immune checkpoint inhibitors demonstrates to nearly fully eradicate a colorectal tumor inside the mouse model by chemotherapy and immunotherapy using the STING pathway.

ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss.

Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide)120 (PPS120), which scavenged ROS and converted to poly(propylene sulfoxide)120 in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.

Evaluation of Mandarin Chinese Speech Recognition in Adults with Cochlear Implants Using the Spectral Ripple Discrimination Test.

BACKGROUND The aim of this study was to explore the value of the spectral ripple discrimination test in speech recognition evaluation among a deaf (post-lingual) Mandarin-speaking population in China following cochlear implantation. MATERIAL AND METHODS The study included 23 Mandarin-speaking adult subjects with normal hearing (normal-hearing group) and 17 deaf adults who were former Mandarin-speakers, with cochlear implants (cochlear implantation group). The normal-hearing subjects were divided into men (n=10) and women (n=13). The spectral ripple discrimination thresholds between the groups were compared. The correlation between spectral ripple discrimination thresholds and Mandarin speech recognition rates in the cochlear implantation group were studied. RESULTS Spectral ripple discrimination thresholds did not correlate with age (r=-0.19; p=0.22), and there was no significant difference in spectral ripple discrimination thresholds between the male and female groups (p=0.654). Spectral ripple discrimination thresholds of deaf adults with cochlear implants were significantly correlated with monosyllabic recognition rates (r=0.84; p=0.000). CONCLUSIONS In a Mandarin Chinese speaking population, spectral ripple discrimination thresholds of normal-hearing individuals were unaffected by both gender and age. Spectral ripple discrimination thresholds were correlated with Mandarin monosyllabic recognition rates of Mandarin-speaking in post-lingual deaf adults with cochlear implants. The spectral ripple discrimination test is a promising method for speech recognition evaluation in adults following cochlear implantation in China.

Interaction of tinnitus suppression and hearing ability after cochlear implantation.

OBJECTIVES: To study the postoperative impact of cochlear implants (CIs) on tinnitus, as well as the impact of tinnitus on speech recognition with CI switched on. METHODS: Fifty-two postlingual deafened CI recipients (21 males and 31 females) were assessed using an established Tinnitus Characteristics Questionnaire and Tinnitus Handicap Inventory (THI) before and after cochlear implantation. The tinnitus loudness was investigated when CI was switched on and off in CI recipients with persistent tinnitus. The relation between tinnitus loudness and recipients' satisfaction of cochlear implantation was analyzed by the visual analogue scale (VAS) score. RESULTS: With CI 'OFF', 42 CI recipients experienced tinnitus postimplant ipsilaterally and 44 contralaterally. Tinnitus was totally suppressed ipsilateral to the CI with CI 'ON' in 42.9%, partially suppressed in 42.9%, unchanged in 11.9% and aggravated in 2.4%. Tinnitus was totally suppressed contralaterally with CI 'ON' in 31.8% of CI recipients, partially suppressed in 47.7%, unchanged in 20.5%. Pearson correlation analysis showed that tinnitus loudness and the results of cochlear implant patients satisfaction was negatively correlated (r = .674, p < .001). CONCLUSION: The study suggests six-month CI activation can be effective for suppressing tinnitus. The tinnitus loudness may affect patients' satisfaction with the use of CI.

A method to induce human cortical long-term potentiation by acoustic stimulation.

OBJECT: Acoustic stimulation induced LTP in the human auditory cortex was successfully recorded for the first time by electroencephalography (EEG) using a stimulus of 1 kHz pure-tone in 2005. However, it was barely reproduced, given considerable challenges to reliably elicit and accurately record the enhanced potentials in vivo. The purpose of this paper was to explore whether acoustic stimuli other than 1 kHz pure-tone could generate LTP or not. MEASURES: To answer this question, we proposed a tetanic-stimulation paradigm of pure-tones, narrow-band noises (NBNs) and white noise (WN) to elicit LTP in human subjects. RESULTS: The results showed that pure-tones with different frequency could elicit LTP in human auditory cortex, and proved for the first time that NBNs and WN could also achieve the same goal. Interestingly, it was also shown that the noises with certain bandwidth induced the greatest LTP and the WN induced LTP had the least variation over time and across subjects in comparison with pure-tones and NBNs. CONCLUSIONS: In light of the results, we suggested to use the paradigm for broader studies of human in vivo cortical plasticity.

[Three applications and the challenge of the big data in otology].

With the expansion of human practical activities, more and more areas have suffered from big data problems. The emergence of big data requires people to update the research paradigm and develop new technical methods. This review discussed that big data might bring opportunities and challenges in the area of auditory implantation, the deafness genome, and auditory pathophysiology, and pointed out that we needed to find appropriate theories and methods to make this kind of expectation into reality.