Aims: The association between serum albumin and depressive symptoms has been unclear in previous epidemiological studies. We explored whether serum albumin is associated with depressive symptoms based on the National Health and Nutrition Examination Survey (NHANES) data. Methods: This cross-sectional study included 13,681 participants aged ≥ 20 years from the NHANES performed during 2005–2018, which produced nationally representative database. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Serum albumin concentration was measured using the bromocresol purple dye method, and participants were divided into quartiles of serum albumin concentrations. Weighted data were calculated according to analytical guidelines. Logistics regression and linear regression models were used to assess and quantify the association between serum albumin and depressive symptoms. Univariate and stratified analyses were also performed. Results: There were 1551 (10.23%) adults (aged ≥ 20 years) with depressive symptoms among the 13,681. A negative association was found between serum albumin concentration and depressive symptoms. Compared with the lowest albumin quartile, the multivariate-adjusted effect size (95% confidence interval) for depressive symptoms of the fully adjusted model in the highest albumin quartile was 0.77 (0.60 to 0.99) and − 0.38 (− 0.66 to − 0.09) using logistics regression and linear regression models respectively. Current smoking status modified the association between serum albumin concentration and PHQ-9 scores (p for interaction = 0.033). Conclusion: This cross-sectional study revealed that albumin concentration is significantly more likely to be a protective factor for depressive symptoms, with the association being more pronounced in non-smokers.

Purpose: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière’s disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable. Methods: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière’s disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere’s Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China. Results: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear. Conclusion: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.

Background: Efficacy of current treatment methods in idiopathic sudden sensorineural hearing loss (ISSNHL) is still unsatisfactory. Objective: This study aimed to discover in differences in effect between steroid applications responsible for promoting the prognosis in ISSNHL. Materials and methods: A study was conducted to diagnose ISSNHL patients in our hospital from January 2014 to September 2016. All patients accepted treatments including intravenous injection (intravenous dexamethasone, [IV DXM]), intratympanic injection (intratympanic methylprednisolone [IT MP], intratympanic dexamethasone [IT DXM]) or combined injections with steroids (IV + IT DXM). Patients were divided into groups according to treatment outcomes and clinical characteristics of each group were compared for univariate comparison. Logistic regression was utilized to verify screening factors from univariate comparison for exclude biases. Results: There were 313 patients with ISSNHL enrolled in the study. Logistic regression verified that vertigo (p = .023), severity of hearing loss (p=.969), pattern of hearing loss (p = .03), and the treatment method (p < .001) were statistically related to the patients’ prognosis based on the condition all biases had been excluded as possible. IT MP showed a better prognosis of hearing improvement compared to treatment with IT DXM (OR = 0.5), IV DXM (OR =0.226), and IV DXM + IV DXM (OR = 0.320). Conclusions and significance: IT MP treatment could be utilized as initial treatment in ISSNHL and might promote outcomes.

Background: Lipid nanoparticles (LNPs) have emerged as the most successful, effective, and safe method for RNA delivery, and have shown tremendous potential for the treatment of various diseases, such as messenger RNA (mRNA) vaccines, gene editing, and RNA interface (RNAi) therapies. The development of novel ionizable lipids holds great promise in improving the efficacy and safety of LNPs. Methods: We synthesized a novel ionizable lipid, ARV-T1, with a cholesterol moiety incorporated in its tail. We characterized the physicochemical properties of LNPs formulated with ARV-T1, calculated the pKa of ARV-T1, and conducted in vitro and in vivo mRNA delivery studies. Results: ARV-T1 has a pKa value of 6.73, and compared to SM-102, the ionizable lipid used in the Moderna SARS-CoV2 vaccine, the LNPs formulated with ARV-T1 showed smaller particle sizes, lower polydispersity indices, and higher absolute zeta potential values. More importantly, the LNPs formulated with ARV-T1 showed significantly increased mRNA delivery both in vitro and in vivo, markedly increased protein expression, and demonstrated more than 10-fold higher potency in inducing SARS-CoV-2 spike protein binding antibodies and SARS-CoV-2 virus neutralizing antibodies in mice compared to the LNPs formulated with SM-102. Furthermore, the unique ester linkage of ARV-T1 enables rapid and complete metabolism in vivo, thereby improving its biocompatibility and safety profile. Conclusion: These findings suggest that the novel ionizable lipid ARV-T1 holds great promise for the development of mRNA vaccines and other mRNA-based therapeutics and may pave the way for the development of safer and more effective mRNA delivery systems.

Autophagy and apoptosis have a complex interplay in the early embryo development. The development of spiral ganglion neurons (SGNs) in addition to Corti’s organ in the mammalian cochlea remains crucial in the first two-week postnatal period. To investigate the roles of apoptosis and autophagy in the development of SGNs, light microscopy was used to observe the morphological changes of SGNs. The number of SGNs was decreased from P1 to P7 and plateaued from P10 to P14. Immunohistochemistry results revealed positive expression of cleaved-caspase3, bcl-2, microtubule-associated protein light chain 3-II (LC3-II), Beclin1, and sequestosome 1 (SQSTM1/P62) in SGNs. The apoptotic bodies and autophagosomes and autolysosomes were also identified by transmission electron microscopy at P1 and P7. Real-time PCR and western blotting results revealed that the apoptotic activity peaked at P7 and the autophagy activity was gradually upregulated along with the development. Taken together, our results for the first time showed that autophagy and apoptosis in SGNs play distinct roles during specific developmental phases in a time-dependent manner.