RESUMO
Background: Post-auricular injection of lidocaine and methylprednisolone sodium succinate is a commonly used treatment for outpatient patients with tinnitus, but it is invasive, painful and has uncertain efficacy. We need to try to replace it with more non-invasive and effective treatments. The 2014 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery recommend the use of cognitive behavioral therapy (CBT) to treat tinnitus. Some clinical doctors have also attempted sound therapy for tinnitus. It is unclear whether sound therapy combined with CBT y is more effective than local injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus. Objective: To evaluate the efficacy and influencing factors of refined sound therapy combined with CBT in the treatment of tinnitus and compare it with post-auricular injection of lidocaine and methylprednisolone sodium succinate. Methods: We recruited 100 patients with tinnitus; ultimately, 81 patients completed the experiment and underwent follow-up. Patients were randomly assigned to either the treatment group (refined sound therapy combined with CBT) or the control group (post-auricular injections of lidocaine and methylprednisolone sodium succinate). Data was collected from 49 patients in the treatment group and 32 patients in the control group. Pre- and post-treatment data were collected using the Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAM-A), Visual Analogue Score (VAS), Tinnitus loudness and Tinnitus Handicap Inventory (THI) score. Comparisons between groups were performed using the chi-square test, Fisher's exact test, or Wilcoxon rank-sum test. All tests were two-sided and considered statistically significant with P < .05. Results: The THI, SDS and HAM-A scores in the treatment group decreased significantly. In the control group, there was a significant reduction in THI scores, but not in SDS and HAM-A scores. In addition, tinnitus loudness and VAS scores were significantly decreased in the 2 groups. There was a significant difference in the reduction of THI, SDS, HAM-A and VAS scores between the 2 groups; the treatment group showed a greater reduction. However, there was no significant difference in the reduction of tinnitus loudness. There was no statistical difference in the reduction of THI scores, SDS scores, VAS scores and tinnitus loudness in different frequency groups, but there was a statistical difference in the reduction of HAM-A scores. There was no statistical difference in the reduction of THI scores, SDS scores, HAM-A scores, VAS scores and tinnitus loudness between patients with and without hearing loss. Conclusions: (1) This new combination is more effective than post-auricular injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus and improving psychological symptoms. The latter had no effect on improving psychological indicators. (2) With this combination, patients with different tinnitus frequencies experienced different improvements in anxiety. (3) Low-frequency tinnitus seems have been more likely to cause sound adaptation. (4) The improvement in tinnitus and anxiety was the same regardless of whether or not there was hearing loss.
RESUMO
BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.