Obesity and septic patient outcomes: Shaping the puzzle through age and sex perspectives.

BACKGROUND & AIMS: While obesity has been reported as a protective factor in septic patients, little is known about the potential modifying effects of age and sex. The objective of this study is to investigate age and sex-specific associations between obesity and the prognosis of septic patients. METHODS: A retrospective analysis was conducted on a cohort of 15,464 septic patients, categorized by body mass index (BMI) into four groups: underweight (<18.5 kg/m2, n = 483), normal (18.5-24.9 kg/m2, n = 4344), overweight (25-29.9 kg/m2, n = 4949) and obese (≥30 kg/m2, n = 5688). Multivariable logistic regression and inverse probability weighting were employed to robustly confirm the protective effect of a higher BMI on 28-day mortality, with normal weight serving as the reference category. Subgroup analyses based on age (young: 18-39, middle-aged: 40-64 and elderly: ≥65) and sex were performed. RESULTS: The findings demonstrate that high BMI independently confers a protective effect against 28-day mortality in septic patients. However, the relationship between BMI and 28-day mortality exhibits a non-linear trend, with a BMI of 34.5 kg/m2 displaying the lowest odds ratio. Notably, the survival benefits associated with a high BMI were not observed in the young group. Moreover, being underweight emerges as an independent risk factor for middle-aged and elderly female patients, while in males it is only a risk factor in the elderly group. Interestingly, being overweight and obese were identified as independent protective factors in middle-aged and elderly male patients, but not in females. CONCLUSIONS: The effect of BMI on mortality in septic patients varies according to age and sex. Elderly individuals with sepsis may derive more prognostic benefits from obesity.

Analysis of characteristics of and risk factors for otological symptoms after COVID-19 infection.

The purpose of this study was to explore the characteristics of and risk factors for otological symptoms after contracting COVID-19. We invited 468 participants who had been infected with COVID-19 to participate in a survey. 310 (66.2%) were women and 158 (33.8%) were men. The mean age is 38.73 (12.21) years. The questionnaire included their basic information, symptoms and symptom duration after SARS-CoV-2 infection, number of vaccine doses received, and details regarding otological symptoms. In total, 106/468 (22.6%) participants experienced tinnitus, 66/468 (14.1%) hearing loss, 103/468 (22.0%) aural fullness, and 71/468 (15.2%) dizziness. Women were more prone to experience tinnitus (P = 0.022) and dizziness (P = 0.001) than men. The group with hearing loss were older (P = 0.025), and their initial COVID-19 symptoms lasted longer (P = 0.028) than those of patients without. Patients with aural fullness were more likely to experience fatigue than patients without (P = 0.002). Patients experiencing dizziness were more likely to experience pharyngalgia (P = 0.040) and fatigue (P = 0.005) than those without. The number of vaccine doses was positively associated with the resolution of otological symptoms (P = 0.035). Multiple logistic regression analysis revealed that sex was an independent risk factor for tinnitus (odds ratio [OR], 1.802; 95% confidence interval [CI], 1.099-2.953; P = 0.020), the duration of initial COVID-19 symptoms for hearing loss (OR, 1.055; 95% CI, 1.008-1.105; P = 0.023), and sex for dizziness (OR, 2.870; 95% CI, 1.489-5.535; P = 0.002). Sex, age, COVID-19-related fatigue, and the duration of initial COVID-19 symptoms may affect the occurrence of otological symptoms, and vaccines may aid their resolution.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

Number of initial symptoms of SARS-CoV-2 infection is associated with the risk of otological symptoms: a retrospective study.

BACKGROUND: The characteristics of otological symptoms in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are lacking. Almost no research has been conducted to explore the emergence of otological symptoms after coronavirus disease 2019 infection. The aims of this study were to investigate the prevalence and specific clinical characteristics of and risk factors for otological symptoms among patients with SARS-CoV-2 infection. METHODS: We included two groups to investigate the prevalence and clinical characteristics of otological symptoms among patients with SARS-CoV-2 infection. The first sample (S1) was drawn retrospectively from four communities via questionnaires, and the second sample (S2) from an outpatient clinic. RESULTS: A total of 189 participants were included in S1 (124 women [65.6%]; mean [standard deviation (SD)] age, 33.66 [13.56] years), and 47 in S2 (25 women [53.2%]; mean [SD] age, 45.28 [14.64] years). The most prevalent otological symptoms in S1 were dizziness (15.9%), tinnitus (7.9%), aural fullness (6.9%), otalgia (5.3%), hearing loss (1.6%), and otopyorrhoea (1.1%). Moreover, for each additional typical symptom of SARS-CoV-2 infection, the risk (odds ratio) of otological symptoms increased by 1.33 (95% confidence interval: 1.10-1.61, p = 0.003). The prevalence of aural fullness was higher in the unvaccinated group than that in the group receiving two or three vaccinations (p = 0.018). CONCLUSIONS: Various otological symptoms may occur in patients with SARS-CoV-2 infection. The number of typical symptoms of SARS-CoV-2 infection is positively associated with the probability of otological symptoms. However, vaccination may reduce the probability of certain otological symptoms.

Polysaccharides: potential bioactive macromolecules for Alzheimer's disease.

Alzheimer's disease (AD) is one of the leading causes of death and disability. AD is a devastating disease that has caused an overwhelming burden. However, no disease-modified treatment was discovered. The approval of sodium oligomannate (GV-971) in mild-moderate AD patients has attracted great attention to investigate the role of saccharides in AD. Therefore, summarizing and explaining the role of saccharides in AD is urgent and promising. Recent studies showed that polysaccharides (PSs) potentially benefit AD in vitro and in vivo. PSs could alleviate the pathological damage and improve cognitive symptoms via (1) antagonizing the toxicity of abnormal amyloid-beta and tau proteins; (2) attenuating oxidative stress and proinflammation; (3) rebuilding neuroplasticity. PSs exhibit one-multiple pathological hits of AD. However, a thorough chemical investigation is needed for further study.

Comprehensive single-cell analysis reveals novel anergic antigen-presenting cell subtypes in human sepsis.

Background: Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the single-cell resolution in sepsis, but a comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted. Methods: All published human scRNA-seq data were downloaded from the single cell portal database. After manually curating the dataset, we extracted all antigen-presenting cells, including dendritic cells (DCs) and monocytes, for identification of cell subpopulations and their gene profiling and intercellular interactions between septic patients and healthy controls. Finally, we further validated the findings by performing deconvolution analysis on bulk RNA sequencing (RNA-seq) data and flow cytometry. Results: Within the traditional DC populations, we discovered novel anergic DC subtypes characterized by low major histocompatibility complex class II expression. Notably, these anergic DC subtypes showed a significant increase in septic patients. Additionally, we found that a previously reported immunosuppressive monocyte subtype, Mono1, exhibited a similar gene expression profile to these anergic DCs. The consistency of our findings was confirmed through validation using bulk RNA-seq and flow cytometry, ensuring accurate identification of cell subtypes and gene expression patterns. Conclusions: This study represents the first comprehensive single-cell analysis of antigen-presenting cells in human sepsis, revealing novel disease-associated anergic DC subtypes. These findings provide new insights into the cellular mechanisms of immune dysregulation in bacterial sepsis.

New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMφs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMφs, they will lead to intestinal disease, such as NEC. This review focuses on the IMφs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMφs in preterm infants, and explores promising therapeutic application for NEC.

Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer's Diseases.

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer's disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.

Pseudolaric acid B triggers cell apoptosis by activating AMPK/JNK/DRP1/mitochondrial fission pathway in hepatocellular carcinoma.

Pseudolaric acid B (PAB), a natural product isolated from the root bark of Pseudolarix kaempferi, has been reported to exert inhibitory effects in various cancers. However, the underlying mechanisms remain largely unclear. In the present study, we investigated the mechanism through which PAB exert its anticancer effects in hepatocellular carcinoma (HCC). PAB inhibited the viability of and induced apoptosis in Hepa1-6 cells in a dose-dependent manner. It disrupted mitochondrial membrane potential (MMP) and impaired ATP production. Furthermore, PAB induced phosphorylation of DRP1 at Ser616 and mitochondrial fission. Blocking DRP1 phosphorylation by Mdivi-1 inhibited mitochondrial fission and PAB-induced apoptosis. Moreover, c-Jun N-terminal kinase (JNK) was activated by PAB, and blocking JNK activity using SP600125 inhibited PAB-induced mitochondrial fission and cell apoptosis. Furthermore, PAB activated AMP-activated protein kinase (AMPK), and inhibiting AMPK by compound C attenuated PAB-stimulated JNK activation and blocked DRP1-dependent mitochondrial fission and apoptosis. Our in vivo data confirmed that PAB inhibited tumor growth and induced apoptosis in an HCC syngeneic mouse model by inducing the AMPK/JNK/DRP1/mitochondrial fission signaling pathway. Furthermore, a combination of PAB and sorafenib showed a synergistic effect in inhibiting tumor growth in vivo. Taken together, our findings highlight a potential therapeutic strategy for HCC.

The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss.

Hearing loss (HL) can be caused by a number of different genetic factors. Non-syndromic HL refers that HL occurs as an isolated symptom in an individual, whereas syndromic HL refers that HL is associated with other symptoms or abnormalities. To date, more than 140 genes have been identified as being associated with non-syndromic HL, and approximately 400 genetic syndromes can include HL as one of the clinical symptoms. However, no gene therapeutic approaches are currently available to restore or improve hearing. Therefore, there is an urgent necessity to elucidate the possible pathogenesis of specific mutations in HL-associated genes and to investigate the promising therapeutic strategies for genetic HL. The development of the CRISPR/Cas system has revolutionized the field of genome engineering, which has become an efficacious and cost-effective tool to foster genetic HL research. Moreover, several in vivo studies have demonstrated the therapeutic efficacy of the CRISPR/Cas-mediated treatments for specific genetic HL. In this review, we briefly introduce the progress in CRISPR/Cas technique as well as the understanding of genetic HL, and then we detail the recent achievements of CRISPR/Cas technique in disease modeling and therapeutic strategies for genetic HL. Furthermore, we discuss the challenges for the application of CRISPR/Cas technique in future clinical treatments.

Combining Serum Procalcitonin Level, Thromboelastography, and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit.

OBJECTIVE: Despite the recent advances in diagnosis and treatment, sepsis continues to lead to high morbidity and mortality. Early diagnosis and prompt treatment are essential to save lives. However, most biomarkers can only help to diagnose sepsis, but cannot predict the development of septic shock in high-risk patients. The present study determined whether the combined measurement of procalcitonin (PCT), thromboelastography (TEG) and platelet (PLT) count can predict the development of septic shock. METHODS: A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021. These patients were divided into two groups: 73 patients who developed septic shock were assigned to the septic shock group, while the remaining 102 patients were assigned to the sepsis group. Then, the demographic, clinical and laboratory data were recorded, and the predictive values of PCT, TEG and PLT count for the development of septic shock were analyzed. RESULTS: Compared to the sepsis group, the septic shock group had statistically lower PLT count and TEG measurements in the R value, K value, α angle, maximum amplitude, and coagulation index, but had longer prothrombin time (DT), longer activated partial thromboplastin time (APTT), and higher PCT levels. Furthermore, the Sequential Organ Failure Assessment (SOFA) score was higher in the septic shock group. The multivariate logistic regression analysis revealed that PCT, TEG and PLT count were associated with the development of septic shock. The area under the curve analysis revealed that the combined measurement of PCT, TEG and PLT count can be used to predict the development of septic shock with higher accuracy, when compared to individual measurements. CONCLUSION: The combined measurement of PCT, TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

Tone perception development in Mandarin-speaking children with cochlear implants.

OBJECTIVE: The purpose of this study was to examine the longer-term effects of cochlear implant (CI) use on tone perception by evaluating improvement in Mandarin tone recognition in children with CIs 2 and 3 years post CI activation, and to explore the effects of implant age, chronological age and duration of CI use on the development of tone perception. METHODS: Tone perception was assessed in 29 bilateral profound hearing impaired children (mean chronological age = 4.6 years, SD = 0.7 years) with unilateral CIs at 24 and 36 months after CI activation using the tone perception subtest in the Mandarin Early Speech Perception (MESP-T) test. RESULTS: Children's tone recognition for tone pairs and individual tones improved significantly between 2 and 3 years post CI use, showing an increase in average tone recognition score from 73.2% to 81.8%, which was significantly higher than chance level (i.e. 50%). There was no significant correlation between tone recognition ability and either implant age or chronological age at two evaluation points. Further analysis revealed that the tone recognition score for tone pair 2-3 was significantly lower than that for other tone pairs except for tone pair 2-4. CONCLUSIONS: Longer CI experience can significantly improve tone recognition ability in CI children between 2 and 3 years post CI activation.

Minimal clinically important difference for the Mandarin version of the Tinnitus Questionnaire determined via anchor-based and distribution-based methods.

BACKGROUND: The previous study showed that the Mandarin Tinnitus Questionnaire (MTQ) has satisfactory reliability and validity. We have also completed the classification of the severity of tinnitus based on MTQ scores. In clinical studies, efficacy is often judged by whether results are statistically significant; however, statistical significance does not necessarily equate to clinical significance, whereas the minimum clinically important difference (MCID) of the scale does. In the following project, we will explore the MCID of the MTQ. METHODS: We recruited participants aged 18 years and above who sought treatment for primary or secondary tinnitus at the Otorhinolaryngology Department of the Hearing Center of West China Hospital, Sichuan University from September 2020 to September 2021. The participants had to undergo the following four assessments of tinnitus severity: doctor evaluation, self-report, the MTQ, and the visual analog scale (VAS), all at baseline and at the follow-up. The MCIDs of the MTQ were established via anchor-based and distribution-based methods. The anchor method used the VAS and self-reported clinical impression as anchors and defined the treatment effectiveness by mean/median and receiver operating characteristic (ROC) curve, while methods of effect size (ES), standard error of measurement (SEM), and reliability change index (RCI) were used in distribution-based methods. RESULTS: A total of 115 patients were investigated in this study, 57.4% of whom were women. The average age was 43.2 ± 13.20 years. The average MTQ and VAS scores at baseline were 31.3 ± 14.90 and 5.03 ± 2.24, respectively, while the average MTQ and VAS scores at follow-up were 15.9 ± 11.70 and 3.58 ± 2.48, respectively. Moreover, in terms of self-reported clinical impressions, 19 patients indicated that they were cured (16.5%), 24 that it was much better (20.9%), 63 that there was no change (54.8%), and 9 that it was much worse (7.8%). The MCIDs for the change in total MTQ ranged from 6.29 to 19.00, those for improvement from 1.09 to 22.75, and those for deterioration from 3.50 to 7.64. CONCLUSION: We selected an absolute value of 7.5 as the MCID for the MTQ score. An increase in MTQ score more than 7.5 was considered aggravation of tinnitus, and a decrease in MTQ score more than 7.5 was considered a reduction in tinnitus.

Global cognitive function is associated with sex, educational level, occupation type, and speech recognition rate in older Chinese adults: a single-center, prospective, cross-sectional study.

BACKGROUND: The development of cognitive impairment may be delayed if its risk factors are identified and detected, if its developmental trend can be predicted, and if early intervention can be performed. This study primarily aimed to investigate the association between global cognitive function and hearing loss, educational level, and occupation type and to determine any differences in such associations according to sex among older Chinese adults. METHODS: In this cross-sectional study, we prospectively recruited 219 individuals above 55 years old in an otolaryngology outpatient clinic who could write independently and had no severe vision impairment. Audiometric examinations included otoscopy, acoustic immittance, pure-tone audiometry, and speech audiometry for each ear. Cognitive function was evaluated by using the Chinese version of the Mini-Mental State Examination (MMSE). Multivariable linear regression analyses were performed to evaluate the relationship between variables and MMSE scores after adjusting for independent variables that were statistically significant in the univariable analyses. RESULTS: We enrolled 219 individuals: 98 men (mean ± standard deviation age, 63.08 ± 6.64 years) and 121 women (62.64 ± 7.17 years). The overall MMSE scores of the normal hearing group and the mild, moderate, and severe-to-profound hearing loss groups were 24.00 (5.00), 24.00 (5.00), 23.00 (5.00), and 23.00 (13.00), respectively. MMSE scores were higher among participants with higher educational levels (p < 0.001) and were significantly correlated with occupation type (p < 0.001). MMSE scores were significantly higher in men than in women (p < 0.001). However, after the analysis of the five subdomains, significant differences were only observed for attention and calculation (p < 0.001) and language (p = 0.011). We further compared the distribution of educational levels between men and women by using the chi-square test; there was no significant difference in educational level between the sexes (p = 0.070). CONCLUSIONS: We reported statistically significant relationships between global cognitive function and sex, educational level, and occupation type. Sex-specific strategies may be required to improve healthcare policies.

Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role of ACSL4 in immune disorders.

Multiple types of regulated cell death (RCD) have been demonstrated to cause gut barrier dysfunction in necrotizing enterocolitis (NEC); however, whether and how ferroptosis is involved in NEC remains unknown. Here, ferroptosis was identified to play a role in NEC using bioinformatics analyses and wet experiments. Inhibition of ferroptosis significantly alleviated NEC in newborn mice. ACSL4 expression levels were augmented and positively correlated with ferroptosis in NEC. Surprisingly, ACSL4 was critically correlated with multiple types of RCD, including autophagy, apoptosis and pyroptosis, as well as hypoxia and inflammation. Besides, ACSL4 was positively correlated with the abundance of multiple types of immune cells, including macrophage, activated dendritic cell, neutrophil and regulatory T cell. Conclusively, we first identified the involvement and role of ferroptosis in NEC and revealed the potential effects of ACSL4 on immune disorders, which could provide a rationale for future research on ferroptosis in NEC.

Heme induces intestinal epithelial cell ferroptosis via mitochondrial dysfunction in transfusion-associated necrotizing enterocolitis.

Transfusion-associated necrotising enterocolitis (TANEC) is a life-threatening disease with a poor prognosis in preterm infants. This study explored whether and how heme induces ferroptosis in TANEC gut injury. A TANEC mouse model and a cell culture system for heme and Caco-2 cells were established. Ferroptosis was assessed by measuring iron and malondialdehyde (MDA) levels and mitochondrial morphology in intestinal tissues and Caco-2 cells. Mitochondrial dysfunction was evaluated by measuring mitochondrial reactive oxygen species (ROS) production and membrane potential using JC-1. The intestinal injury grade was higher in the anemia-transfusion group than in the control group (p < .0001). Higher intestinal iron concentration (p < .0001), elevated levels of lipid peroxidation MDA (p = .0021), and ferroptotic mitochondrial morphological changes were found in mice of the anemia-transfusion group; specific ferroptosis inhibitor could alleviate anemia-transfusion gut injury, suggesting that ferroptosis play a role in the TANEC gut injury. Next, we explored whether heme released by hemolysis of erythrocytes induces ferroptosis in intestinal epithelial cells in vitro. The viability of Caco-2 cells significantly decreased after heme treatment (p < .0001). Iron accumulation, MDA elevated levels, and mitochondrial dysfunction also existed in the co-culture system, which ferroptosis inhibitors could reduce. In summary, ferroptosis was discovered in TANEC, and heme could induce ferroptosis in intestinal epithelial cells via mitochondrial dysfunction. Heme-inducing ferroptosis may be a possible mechanism and therapeutic target for TANEC.

Baicalein ameliorates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via regulating GPX4/ACSL4/ACSL3 axis.

Accumulating evidence have indicated that ferroptosis plays a crucial role in cerebral ischemia-reperfusion (I/R) injury which is the most serious treatment complication of ischemic stroke. Baicalein (5,6,7-trihydroxyflavone) is a main bioactive ingredient isolated from a traditional Chinese medicine named Baikal Skullcap, which is the root of Scutellaria baicalensis Georgi. This study investigated the potential role of baicalein in cerebral I/R injury using oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells, transient middle cerebral artery occlusion (tMCAO) mice and RSL3-sitmulated HT22 cells. Baicalein improved the viability of OGD/R cells and significantly ameliorated cerebral I/R injury in tMCAO mice. Baicalein decreased the iron levels, lipid peroxidation production and morphology features of ferroptosis of the brain tissues in tMCAO mice, which indicated that baicalein ameliorated cerebral I/R injury by inhibiting ferroptosis in vivo and in vitro. We further confirmed that baicalein had the activity of inhibiting ferroptosis in RSL3-stimulated HT22 cells. Western blot revealed that baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral I/R injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. The results suggested that baicalein has therapeutic potential as a drug for cerebral I/R injury.

Exploring the Association of Leukocyte Telomere Length and Hearing Threshold Shifts of Adults in the United States.

Background: Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States. Methods: A total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999-2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels. Results: The mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted ß-21.45, 95% CI -37.28, -5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted ß0.18, 95% CI -2.21, 2.57; P = 0.8809). Conclusion: Our findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.

Early detection of noise-induced hearing loss.

BACKGROUND: Noise-induced hearing loss (NIHL) is the second most common acquired hearing loss following presbycusis. Exposure to recreational noise and minimal use of hearing protection increase the prevalence of NIHL in young females. NIHL is irreversible. Identifying minor hearing pathologies before they progress to hearing problems that affect daily life is crucial. AIM: To compare the advantages and disadvantages of extended high frequency (EHF) and otoacoustic emission and determine an indicator of hearing pathologies at the early sub-clinical stage. METHODS: This cross-sectional study was implemented in West China Hospital of Sichuan University from May to September 2019. A total of 86 participants, aged 18-22 years, were recruited to establish normative thresholds for EHF. Another 159 adults, aged 18-25 years with normal hearing (0.25-8 kHz ≤ 25 dBHL), were allocated to low noise and noise exposure groups. Distortion otoacoustic emission (DPOAE), transient evoked otoacoustic emissions (TEOAE), and EHF were assessed in the two groups to determine the superior technique for detecting early-stage noise-induced pathologies. The chi-square test was used to assess the noise and low noise exposure groups with respect to extended high-frequency audiometry (EHFA), DPOAE, and TEOAE. P ≤ 0.05 was considered statistically significant. RESULTS: A total of 86 participants (66 females and 20 males) aged between 18 and 22 (average: 20.58 ± 1.13) years were recruited to establish normative thresholds for EHF. The normative thresholds for 9, 10, 11.2, 12.5, 14, 16, 18, and 20 kHz were 15, 10, 20, 15, 15, 20, 28, and 0 dBHL, respectively. A total of 201 participants were recruited and examined for eligibility. Among them, 159 adults aged between 18 and 25 years were eligible in this study. No statistical difference was detected between the noise exposure and the low noise exposure groups using EHFA, DPOAE, and TEOAE (P > 0.05) except in the right ear at 4 kHz using TEOAE (abnormal rate 20.4% vs 5.2%, respectively; P = 0.05). CONCLUSION: These results showed TEOAE as the earliest indicator of minor pathology compared to DPOAE and EHFA. However, a multicenter controlled study or prospective study is essential to verify these results.