Refined Sound Therapy in Combination with Cognitive Behavioural Therapy to Treat Tinnitus: A Randomized Controlled Trial.

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.

Psychological outcomes of the systematic interventions based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer: A randomized clinical trial.

BACKGROUND: Psychological distress is a multi-factorial unpleasant experience of a psychological, social, spiritual, and/or physical nature that may interfere with one's ability to cope effectively with cancer, physical symptoms and treatment. Psychological distress is common and affects the prognosis of cancer patients. Lung cancer accounted for 11.4 % of all new cancer cases and 18 % of all cancer mortality for 36 cancers in 185 countries. The prevalence of distress among Chinese lung cancer patients ranged from 10.1 % to 61.29 %. However, the existing intervention studies on the psychological distress in lung cancer patients are limited and intervention results may be different. OBJECTIVES: To explore the psychological outcomes of a nurse-led systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer undergoing operation at anxiety and depression. DESIGN: A randomized clinical trial. SETTING: Thoracic surgery ward in a tertiary hospital in China. PARTICIPANTS: Lung cancer patients undergoing surgery. METHODS: This is a 12-month longitudinal randomized controlled study in a tertiary hospital in China. A total of 240 lung cancer patients were randomly divided into either the control group or the intervention group. The nurse-led systematic intervention contents include psychological education, intervention measures based on the stress-induced situation, affective, bodily, and cognitive reactions framework, issuance of daily lifestyle cards, and regular follow-ups. The Hospital Anxiety and Depression Scale, Functional Assessment of Chronic Illness Therapy-Fatigue Scale, and Satisfaction with Life Scale were used for the baseline assessment within 48 h upon admission. The same assessment was performed respectively at 1, 3, 6 and 12 months after the intervention started. The effects of the systematic interventions on depression, anxiety, fatigue, and life satisfaction were tested by a linear mixed effects model. RESULTS: Overall time-by-group interaction effects were significantly different with regard to anxiety, depression, and fatigue after controlling for the covariates, while a significant time-by-group interaction effect was not found for life satisfaction. Changes for anxiety and depression scores at 6 and 12 months after initiation of the intervention were significantly greater in the intervention group compared with those in the control group (t = 3.046, p = 0.002, t = 3.190, p = 0.001; t = 3.735, p = 0.000, t = 2.979, p = 0.002), whereas scores for fatigue were significantly higher in the intervention group at 6 and 12 months (t = -3.096, p = 0.002, t = -2.784, p = 0.005). CONCLUSION: The systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework may effectively relieve anxiety, depression, and fatigue in lung cancer patients undergoing surgery. REGISTRATION: This study was registered on December 22, 2019 with the registration number ChiCTR1900028487, and the date of first recruitment was Jan 5, 2020.

Therapeutic adenine base editing of human hematopoietic stem cells.

In ß-thalassemia, either γ-globin induction to form fetal hemoglobin (α2γ2) or ß-globin repair to restore adult hemoglobin (α2ß2) could be therapeutic. ABE8e, a recently evolved adenine base editor variant, can achieve efficient adenine conversion, yet its application in patient-derived hematopoietic stem cells needs further exploration. Here, we purified ABE8e for ribonucleoprotein electroporation of ß-thalassemia patient CD34+ hematopoietic stem and progenitor cells to introduce nucleotide substitutions that upregulate γ-globin expression in the BCL11A enhancer or in the HBG promoter. We observed highly efficient on-target adenine base edits at these two regulatory regions, resulting in robust γ-globin induction. Moreover, we developed ABE8e-SpRY, a near-PAMless ABE variant, and successfully applied ABE8e-SpRY RNP to directly correct HbE and IVS II-654 mutations in patient-derived CD34+ HSPCs. Finally, durable therapeutic editing was produced in self-renewing repopulating human HSCs as assayed in primary and secondary recipients. Together, these results support the potential of ABE-mediated base editing in HSCs to treat inherited monogenic blood disorders.

CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric ß0/ß0 transfusion-dependent ß-thalassemia.

Gene editing to disrupt the GATA1-binding site at the +58 BCL11A erythroid enhancer could induce γ-globin expression, which is a promising therapeutic strategy to alleviate ß-hemoglobinopathy caused by HBB gene mutation. In the present study, we report the preliminary results of an ongoing phase 1/2 trial (NCT04211480) evaluating safety and efficacy of gene editing therapy in children with blood transfusion-dependent ß-thalassemia (TDT). We transplanted BCL11A enhancer-edited, autologous, hematopoietic stem and progenitor cells into two children, one carrying the ß0/ß0 genotype, classified as the most severe type of TDT. Primary endpoints included engraftment, overall survival and incidence of adverse events (AEs). Both patients were clinically well with multilineage engraftment, and all AEs to date were considered unrelated to gene editing and resolved after treatment. Secondary endpoints included achieving transfusion independence, editing rate in bone marrow cells and change in hemoglobin (Hb) concentration. Both patients achieved transfusion independence for >18 months after treatment, and their Hb increased from 8.2 and 10.8 g dl-1 at screening to 15.0 and 14.0 g dl-1 at the last visit, respectively, with 85.46% and 89.48% editing persistence in bone marrow cells. Exploratory analysis of single-cell transcriptome and indel patterns in edited peripheral blood mononuclear cells showed no notable side effects of the therapy.

Simulation stress model of the undersea environment activates the central nervous, neuroendocrine and immune systems and anxiety in rats.

The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine.

Pre-surgery beliefs about pain and surgery as predictors of acute and chronic post-surgical pain: A prospective cohort study.

BACKGROUND: Chronic pain post-surgical pain (CPSP) is common and has far-reaching negative consequences for patients, yet relatively few studies have evaluated the impact of both deficit- and resource-based beliefs about pain and surgery on subjective intensities of acute and chronic post-surgical pain. To address this issue a prospective cohort study was performed. METHOD: 259 consecutive surgery patients from general surgery, gynecology, and thoracic departments completed a self-report battery of demographics, pain experiences, and psychological factors 24 h before surgery (T1) and provided follow-up pain intensity ratings 48 h-72 h after surgery (T2), and at a 4-month follow-up (T3). RESULTS: In the hierarchical regression model for acute post-operative pain intensity, pre-surgery pain self-efficacy beliefs made a significant unique contribution independent of all other pre-surgery and surgery-related factors (i.e., age, presence of pre-surgical pain, type of anesthesia, surgery duration). In the prediction model for intensity of chronic post-surgical pain, beliefs about long-term effects of surgery had a unique impact after controlling other significant pre-surgery and surgery influences (gender, education, surgery time). CONCLUSION: Results underscored the potential utility of considering specific pre-surgery pain- and surgery-related beliefs as factors that predict patient experiences of acute and chronic post-operative pain.

Identifying At-Risk Subgroups for Acute Postsurgical Pain: A Classification Tree Analysis.

Objective: Acute postsurgical pain is common and has potentially negative long-term consequences for patients. In this study, we evaluated effects of presurgery sociodemographics, pain experiences, psychological influences, and surgery-related variables on acute postsurgical pain using logistic regression vs classification tree analysis (CTA). Design: The study design was prospective. Setting: This study was carried out at Chongqing No. 9 hospital, Chongqing, China. Subjects: Patients (175 women, 84 men) completed a self-report battery 24 hours before surgery (T1) and pain intensity ratings 48-72 hours after surgery (T2). Results: An initial logistic regression analysis identified pain self-efficacy as the only presurgery predictor of postoperative pain intensity. Subsequently, a classification tree analysis (CTA) indicated that lower vs higher acute postoperative pain intensity levels were predicted not only by pain self-efficacy but also by its interaction with disease onset, pain catastrophizing, and body mass index. CTA results were replicated within a revised logistic regression model. Conclusions: Together, these findings underscored the potential utility of CTA as a means of identifying patient subgroups with higher and lower risk for severe acute postoperative pain based on interacting characteristics.

Microarray analysis and phenotypic response of Pseudomonas aeruginosa PAO1 under hyperbaric oxyhelium conditions.

Pseudomonas aeruginosa is an important opportunistic pathogen associated with multiple diseases including cystic fibrosis and nosocomial infections. Pseudomonas aeruginosa is also the microbe most often isolated from ear and skin infections in divers. Saturation divers often suffer from various skin and mucous disorders, of which P. aeruginosa infections are the most serious and frequent. Previous studies mainly focused on adaptive and regulatory mechanisms of P. aeruginosa virulence in inducing clinical acute and chronic infections under different environmental conditions. However, there are few studies describing the physiological adaptive and regulatory mechanisms of P. aeruginosa in inducing high infectivity in healthy divers under hyperbaric oxyhelium conditions and even fewer studies describing the overall influence of the hyperbaric oxyhelium environment on regulating mRNA and protein expression levels of P. aeruginosa. The present study used transcriptomic and virulence phenotype analysis to identify factors that allow P. aeruginosa to become established in a hyperbaric oxyhelium environment to facilitate infections in divers. Transcriptional profiling of P. aeruginosa grown under steady-state hyperbaric oxyhelium stress conditions showed an upregulation of genes associated with stress-sense/response, protein folding, transcriptional regulation, pili and flagellum metabolism, virulence adaptation, and membrane protein metabolism. Some of these genes (including several two-component systems not previously known to be influenced by hyperbaric oxyhelium) were differentially expressed by P. aeruginosa in response to 72 h of exposure to hyperbaric oxyhelium stress. Detection of the virulence phenotype confirmed the results of cDNA microarrays. Based on these results, we conclude that hyperbaric oxyhelium conditions affect PAO1 gene expression and upregulate the expression of most virulence genes. The data obtained in our study may provide new insight into the molecular mechanism of hyperbaric oxyhelium exposure against P. aeruginosa virulence adaptation.

[The effects of cell growth factors on proliferation and migration of coronary artery endothelial cells].

AIM: To study the effects of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) on proliferation and migration of bovine coronary artery endothelial cells (BCAEC) in vitro. METHODS: BCAECs were isolated and cultured in vitro, and divided into control group, VEGF group and HGF group. BCACEs proliferation were measured using MTT, and their migration was observed using reverse microscope. RESULTS: The OD value of control, VEGF and HGF group were 0.22 +/- 0.01, 0.40 +/- 0.14, 0.44 +/- 0.15 respectively. The proliferation ratio of BCAECs in VEGF and HGF group was 81.8% +/- 16.9%, 100.0% +/- 21.1% respectively. There was no migration in control group, but significant migration in VEGF and HGF group. CONCLUSION: Both VEGF and HGF can promote proliferation and migration of BCAECs, the effect of HGF is stronger than VEGF.