Impact of hyperlipidemia as a coexisting factor on the prognosis of idiopathic sudden sensorineural hearing loss: A propensity score matching analysis.

OBJECTIVE: To define the impact of hyperlipidemia as a coexisting factor on the prognosis of Idiopathic Sudden Sensorineural Hearing Loss (ISSHL), we prospectively analysed the Lipid-lowering therapy Group (LLTG) data compared with Control Group (CG) data to determine the effects of Lipid intervention on the prognosis of sudden hearing loss. DESIGN: A prospective, non-randomized study. SETTING: Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China. PARTICIPANTS: A total of 653 in-patient SSHL patients were enrolled between January 2014 to August 2018. MAIN OUTCOME MEASURES: From January 2014 to August 2018, 653 patients with ISSHL who also had hyperlipidemia as coexisting factor were identified. Patients enrolled in LLTG (n = 200) or CG (n = 453) were compared by a propensity score matching analysis (PSM, caliper = 0.01, n = 2) to balance pre-existing clinical characteristics. After matching, the effective rate of different hyperlipidemia types and different types of audiogram in both groups were performed by Cochran-Mantel-Haenszel test (CMH). RESULTS: After PSM, 440 patients were studied (146 in LLTG, 294 in CG), and the influence of interference factors was balanced, meanwhile, the final hearing level was better in LLTG than CG (P = .043), and hearing gain was higher in LLTG than CG (P = .006). Cure rate (32.9%), significant improvement rate (22.6%) and the total effective rate (76.0%) in LLTG were better than that in CG group (26.5%, 15.6% and 63.6%) after the Pearson chi-square test (P < .05). Analysis with the Cochran-Mantel-Haenszel test showed that the total effective rate was better in LLTG than CG respectively (P = .009) in each different hyperlipidemia types, and there were statistically significant differences in TG higher group (TG Group; P = .018). Moreover, the total effective rate was better in LLTG than CG (P = .006) for all patterns of audiogram, and there were statistically significant differences in flat audiogram (P = .043). CONCLUSIONS: Lipid-lowering therapy can improve the curative effect of sudden hearing loss patients combined with hyperlipidemia. There was a significant difference in the total effective rate of TG Group after lipid intervention, suggesting that there might be causal relationship between TG and sudden hearing loss. There was a significant difference in the total effective rate between flat audiogram, which may suggest flat hearing loss was more likely caused by vascular dysfunction.

Bacterial magnetosomes as an efficient gene delivery platform for cancer theranostics.

BACKGROUND: Gene therapy has gained an increasing interest in its anti-tumor efficiency. However, numerous efforts are required to promote them to clinics. In this study, a novel and efficient delivery platform based on bacterial magnetosomes (BMs) were developed, and the efficiency of BMs in delivering small interfering ribonucleic acid (siRNA) as well as antiproliferative effects in vitro were investigated. RESULTS: Initially, we optimized the nitrogen/phosphate ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the BMs-PEI-siRNA composites. Furthermore, the prepared nanoconjugates were systematically characterized. The dynamic light scattering measurements indicated that the particle size and the zeta potential of BMs-PEI-siRNA are 196.5 nm and 49.5 ± 3.77 mV, respectively, which are optimum for cell internalization. Moreover, the confocal laser scanning microscope observations showed that these composites were at a proximity to the nucleus and led to an effective silencing effect. BMs-PEI-siRNA composites efficiently inhibited the growth of HeLa cells in a dose-as well as time-dependent manner. Eventually, a dual stain assay using acridine orange/ethidium bromide, revealed that these nanocomposites induced late apoptosis in cancer cells. CONCLUSIONS: A novel and efficient gene delivery system based on BMs was successfully produced for cancer therapy, and these innovative carriers will potentially find widespread applications in the pharmaceutical field.

Prognostic changes after sudden deafness in patients with inner ear malformations characterized by LSCC: a retrospective study.

Introduction: This study aimed to investigate the clinical features and prognosis of sudden sensorineural hearing loss in patients with lateral semicircular canal (LSCC) malformation. Methods: This study enrolled patients with LSCC malformation and sudden sensorineural hearing loss (SSNHL) who were admitted to Shandong ENT Hospital between 2020 and 2022. We collected and analyzed data on examinations of audiology, vestibular function, and imaging records of patients and summarized the clinical characteristics and prognosis of these patients. Results: Fourteen patients were enrolled. Patients with LSCC malformation was noted in 0.42% of all SSNHL cases during the same period. One patients had bilateral SSNHL and the rest had unilateral SSNHL. Of them, eight and six patients had unilateral and bilateral LSCC malformations, respectively. Flat hearing loss was noted in 12 ears (80.0%) and severe or profound hearing loss was noted in 10 ears (66.7%). After treatment, the total efficacy rate of SSNHL with LSCC malformation was 40.0%. Vestibular function was abnormal in all patients, but only five patients (35.7%) had dizziness. There were statistically significant differences in the vestibular functions between patients with LSCC malformation and matched patients without the malformation hospitalized during the same period (p < 0.05). Conclusion: Patients with SSNHL and LSCC malformation had flat-type and severe hearing loss and worse disease prognosis compared to those with SSNHL without LSCC malformation. Vestibular function is more likely to be abnormal; however, there was no significant difference in vestibular symptoms between patients with and without LSCC malformation. LSCC is a risk factor for the prognosis of SSNHL.

Idiopathic Sudden Sensorineural Hearing Loss in Different Ages: Prognosis of Patients With Initial Total Hearing Loss.

Objective: This study aimed to analyze the hearing improvement and prognosis factors of idiopathic sudden sensorineural hearing loss (ISSNHL) in different ages with initial total hearing loss. Methods: We reviewed the medical records of 5,711 hospitalized patients with ISSNHL from 2016 to 2021 in our center. All of the patients had been treated with uniform combination drug therapy. After excluding the patients with initial partial hearing loss and those diagnosed with clear etiology, 188 patients were enrolled in this study and divided into six age groups (18-30, 31-40, 41-50, 51-60, 61-70, ≥ 71 years). In all groups, decreases in pure-tone average (PTA) 1 month posttreatment, effective rate, and clinical characteristics (vertigo, tinnitus, hospital stay, comorbidity, and inner ear magnetic resonance imaging) were analyzed. Results: Among the 188 enrolled patients, 86% had vertigo. Complete recovery was seen in 0.5% of patients, and marked recovery was seen in 43% of patients. The mean 1 month posttreatment PTAs were as follows: 18-30 years: 80 ± 7.5 dB; 31-40 years: 100 ± 9.0 dB; 41-50 years: 99 ± 8.3 dB; 51-60 years: 101 ± 8.6 dB; 61-70 years: 96 ± 9.6 dB; and ≥ 71 years: 88 ± 13.0 dB. Compared with the other groups, the 18-30- years group showed better recovery of hearing threshold in five frequencies (0.25, 0.5, 1, 2, and 4 kHz, respectively, at octave or semioctave frequencies under air conduction), and the recovery of hearing threshold at 0.25 and 0.5 Hz was better than the recovery at 1, 2, and 4 kHz. According to the results of the chi-square test statistical analysis, vertigo and comorbidities were associated with a poor prognosis of ISSNHL. Conclusion: In summary, the treatment outcomes of patients with ISSNHL with initial total hearing loss were poor. There was a significant age-related difference with respect to marked recovery 1 month posttreatment, and the 18-30- years group showed better recovery than the other age groups.

The influence of spatial distribution on add-on therapy of designed Ca-Alg/CS MEMs system.

To improve the efficacy and reduce the systemic toxicity of the diabetes mellitus, herewith, we developed a novel microparticles-embedded microcapsules (MEMs) system, synthesized from calcium alginate/chitosan (Ca-Alg/CS), by emulsion gelation using a high voltage electrostatic droplet generator. In our study, we selected two antidiabetic drugs insulin (INS) and metformin (MET) as model drugs to investigate different spatial distribution appropriate of MEMs system. Characterization based on particle size and morphology, encapsulation efficiency and drug loading, as well as drug delivery properties were carried out on the MEMs system. Typical multi-chamber structure was shown by SEM and the optical spectra. The average diameters of microparticles and Ca-Alg/CS MEMs were 2100 nm and 410 µm, respectively. Insulin and MET were embedded into MEMs via electrostatic reaction according to FT-IR spectra. Moreover, drug loading and encapsulation efficiency of INS were higher than that of MET in this system when drugs were loaded alone or together. More importantly, this system has potential for orderly drug release and well sustained release when MET in the inner and INS in the outer space could be applied as a combination therapy for diabetes. The obtained in vivo experimental data on diabetes rats has shown that the designed MEMs system resulted in a higher hypoglycemic effect within add-on therapy.

Bacterial magnetosomes-based nanocarriers for co-delivery of cancer therapeutics in vitro.

In recent times, co-delivery of therapeutics has emerged as a promising strategy for treating dreadful diseases such as cancer. MATERIALS AND METHODS: In this study, we developed a novel nanocarrier based on bacterial magnetosomes (BMs) that co-loaded with siRNA and doxorubicin (DOX) using polyethyleneimine (PEI) as a cross-linker (BMs/DP/siRNA). The delivery efficiency of siRNA as well as the pH-responsive release of DOX, and synergistic efficacy of these therapeutics in vitro were systematically investigated. RESULTS: The structure of DOX-PEI (DP) conjugates that synthesized via hydrazone bond formation was confirmed by 1H nuclear magnetic resonance (NMR). The in vitro release experiments showed that the DP conjugate (DOX-loading efficiency - 5.77%±0.08%) exhibited the long-term release behavior. Furthermore, the optimal BMs/DP/siRNA particle size of 107.2 nm and the zeta potential value of 31.1±1.0 mV facilitated enhanced cellular internalization efficiency. Moreover, the agarose gel electrophoresis showed that the co-delivery system could protect siRNA from degradation in serum and RNase A. In addition, the cytotoxicity assay showed that BMs/DP/siRNA could achieve an excellent synergistic effect compared to that of siRNA delivery alone. The acridine orange (AO)/ethidium bromide (EB) double staining assay also showed that BMs/DP/siRNA complex could induce cells in a stage of late apoptosis and nanocomplex located in the proximity of the nucleus. CONCLUSION: The combination of gene and chemotherapeutic drug using BMs is highly efficient, and the BMs/DP/siRNA would be a promising therapeutic strategy for the future therapeutics.

A Natural Bacterium-Produced Membrane-Bound Nanocarrier for Drug Combination Therapy.

To minimize the non-specific toxicity of drug combination during cancer therapy, we prepared a new system synthesized from bacteria to deliver the anticancer drugs cytosine arabinoside (Ara-C) and daunorubicin (DNR). In this study, we selected genipin (GP) and poly-l-glutamic acid (PLGA) as dual crosslinkers. Herewith, we demonstrated the preparation, characterization and in vitro antitumor effects of Ara-C and DNR loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ADBMs-P). The results show that this new system is stable and exhibits optimal drug-loading properties. The average diameters of BMs and ADBMs-P were 42.0 ± 8.6 nm and 65.5 ± 8.9 nm, respectively, and the zeta potential of ADBMs-P (-42.0 ± 6.4 mV) was significantly less than that of BMs (-28.6 ± 7.6 mV). The optimal encapsulation efficiency and drug loading of Ara-C were 68.4% ± 9.4% and 32.4% ± 2.9%, respectively, and those of DNR were 36.1% ± 2.5% and 17.9% ± 1.6%. Interestingly, this system also exhibits long-term release behaviour sequentially, without an initial burst release. The Ara-C drug continued to release about 85% within 40 days, while DNR release lasted only for 13 days. Moreover, similar to free drugs, ADBMs-Ps are strongly cytotoxic to cancer cells in vitro (HL-60 cells), with the inhibition rate approximately 96%. This study reveals that this new system has a potential for drug delivery application in the future, especially for combination therapy.

Preparation and in vitro antitumor effects of cytosine arabinoside-loaded genipin-poly-l-glutamic acid-modified bacterial magnetosomes.

To solve the problem of synthesized magnetic nanoparticles in cancer therapy, a new drug delivery system synthesized from bacteria was used to load cytosine arabinoside (Ara-C). Genipin (GP) and poly-l-glutamic acid (PLGA) were selected as dual cross-linkers. The preparation and characterization of Ara-C-loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ABMs-P), as well as their in vitro antitumor effects, were all investigated. Transmission electron micrographs (TEM) and Fourier transform infrared (FTIR) spectroscopy suggested that Ara-C could be bound to the membrane of BMs modified by GP-PLGA. The diameters of the BMs and ABMs-P were 42.0±8.6 nm and 74.9±8.2 nm, respectively. The zeta potential revealed that the nanoparticles were stable. Moreover, this system exhibited optimal drug-loading properties and long-term release behavior. The optimal encapsulation efficiency and drug-loading were 64.1%±6.6% and 38.9%±2.4%, respectively, and ABMs-P could effectively release 90% Ara-C within 40 days, without the release of an initial burst. In addition, in vitro antitumor experiments elucidated that ABMs-P is cytotoxic to HL-60 cell lines, with an inhibition rate of 95%. The method of coupling drugs on BMs using dual cross-linkers is effective, and our results reveal that this new system has potential applications for drug delivery in the future.