Deletion of Bmal1 in aggrecan-expressing cells leads to mouse temporomandibular joint osteoarthritis.

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

Development of the West China Tinnitus Impact Inventory and Analysis of Its Reliability and Validity.

OBJECTIVES: Owing to differences in cultural background, education level, and lifestyle, certain items of existing tinnitus evaluation scales are difficult for Chinese patients to understand, despite being translated. However, few independently developed scales have been developed specifically for Chinese patients. Therefore, with this study, we aimed to construct a tinnitus scale, the West China Tinnitus Impact Inventory (WCTII), suitable for the accurate reflection of the impact and severity of the disease in this population. DESIGN: Basic items were obtained through semistructured interviews with patients with tinnitus. We invited 23 domestic experts on tinnitus to form an expert group. The basic items were modified using the Delphi method. Cronbach's α values for the scale scores and correlation coefficients between the items and the scale scores were calculated. Items with correlation coefficients <0.5 were deleted. Exploratory factor analysis was conducted to determine the scale structure of the items remaining after item deletion. The intragroup correlation coefficient was used to assess the scale's test-retest reliability. The Pearson correlation coefficient between the scale scores and the scores for the Chinese-Mandarin version of the Tinnitus Handicap Inventory was used to evaluate concurrent validity. RESULTS: After five rounds of expert correspondence and exploratory factor analysis, we determined the content and structure of the scale. The WCTII consists of 19 items in 4 subscales, namely, F1: the impact of tinnitus on emotion (items 1 to 9); F2: the impact of tinnitus on sleep (items 10 to 12); F3: patients' beliefs about their tinnitus (items 13 to 16, 19); and F4: the impact of tinnitus on auditory processing ability (items 17 to 18). The overall Cronbach's α was 0.934. The Cronbach's α values for F1 to F4 were 0.912, 0.843, 0.829, and 0.838, respectively. The intragroup correlation coefficient (95% confidence interval) of the total scale and F1 to F4 were 0.779 (0.549 to 0.886), 0.738 (0.496 to 0.860), 0.826 (0.713 to 0.897), 0.720 (0.536 to 0.836), and 0.715 (0.532 to 0.832), respectively. The correlation between the WCTII and Chinese-Mandarin version of the Tinnitus Handicap Inventory scores was 0.849 (p < 0.001). CONCLUSIONS: The WCTII yielded satisfactory reliability and validity, indicating that it can be used to assess the severity of tinnitus in Chinese patients.

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.

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.

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.

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.

Investigation on chronic tinnitus efficacy of combination of non-repetitive preferred music and educational counseling: a preliminary study.

PURPOSE: To improve the efficacy of music therapy on tinnitus relief, specific music that was not repetitively played and satisfies individualized preference was developed. The aim of this study was to investigate effects of combination of the specific music and educational counseling on tinnitus relief in short term. METHODS: Sixty patients suffering from chronic tinnitus were included. The non-randomized controlled study was designed with two intervention groups: educational counseling (EC, which included a 1-h individualized instruction) and preferred music therapy [PMT, which included EC plus 15, 30-min preferred music sessions (PMS)]. Three assessments-the Chinese-Mandarin version of Tinnitus Handicap Inventory (THI-CM), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analogue Scale (VAS) were administered before and 1, 2, 3 weeks after initiation of treatment to evaluate the efficacy. RESULTS: Twenty-six patients in PMT group attained a clinically meaningful improvement in THI compared to 15 in the EC group, though both groups achieved a statistically relevant reduction in the 3 assessments. CONCLUSION: The PMT had a positive impact on chronic tinnitus and related distress in a short term. It outperformed the separate EC, which is an appropriate treatment option in clinic. Therefore, it presents a possible complement to the therapeutic spectrum in chronic tinnitus. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022624. Registered on 19 April 2019.

The anti-breast cancer property of physcion via oxidative stress-mediated mitochondrial apoptosis and immune response.

CONTEXT: Physcion (Phy) exerts several pharmacological effects including anti-inflammatory, antioxidant, and antitumor properties. OBJECTIVE: This study investigates the cytotoxicity and its underlying mechanisms of Phy on breast cancer. MATERIALS AND METHODS: Human breast cancer cell MCF-7 was treated with 5-400 µM Phy for 24 h, MCF-7-xenografted BALB/c nude mice and immunosuppressive mice model induced by cyclophosphamide were intraperitoneally injected with 0.1 mL/mouse normal saline (control group) and 30 mg/kg Phy every other day for 14 or 28 days, and pathological examination, ELISA and western blot were employed to investigate the Phy anti-breast cancer property in vitro and in vivo. RESULTS: In MCF-7 cells, Phy 24 h treatment significantly reduced the cell viability at dose of 50-400 µM and 24 h, with an IC50 of 203.1 µM, and 200 µM Phy induced 56.9, 46.9, 36.9, and 46.9% increment on LDH and caspase-3, -8 and -9. In MCF-7-xenograft tumour nude mice and immunosuppressive mice, 30 mg/kg Phy treatment inhibited tumour growth from the 8th day, and reduced Bcl-2 and Bcl-xL >50%, HO-1 and SOD-1 > 70% in tumour tissues of immunosuppressive mice. In addition, Phy reduced nuclear factor erythroid 2-related factor 2 > 30% and its downstream proteins, and enhanced the phosphorylation of nuclear factor-kappa B > 110% and inhibitor of NF-кB α > 80% in the tumour tissues of BALB/c mice. DISCUSSION AND CONCLUSIONS: This research demonstrated that Phy has an anti-breast cancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which provides a scientific basis for further research on its clinical applications.

Pulsatile Tinnitus Caused by Internal Jugular Phlebectasia in an Adult.

Internal jugular phlebectasia is a rare condition. Children with internal jugular phlebectasia are often discovered by their parents when they notice a soft mass in the neck that appears when the child cries, coughs, or breathes deeply. Most internal jugular vein dilatations occur unilaterally on the right side according to the literature reports. To our knowledge, no other internal jugular phlebectasia patients reported pulsatile tinnitus as the major complaint without a soft mass in the neck. The authors reported a female adult patient with left-side internal jugular phlebectasia with pulsatile tinnitus as the major complaint without a soft mass in the neck. Internal jugular phlebectasia was diagnosed by color ultrasound of the internal jugular vein. Pure-tone audiometry, tympanometry, hemoglobin, thyroid function, and magnetic resonance imaging were made to differentiate other diseases that can cause the pulsatile tinnitus. Conservative treatment is recommended in this report. The possibility of internal jugular vein dilatation should be considered when differentiate the possible diseases that caused pulsatile tinnitus.

Optimization extraction and bioactivities of polysaccharide from wild Russula griseocarnosa.

The extraction conditions and biological activities of polysaccharides from wild Russula griseocarnosa (PRG) were investigated. Response Surface Methodology (RSM) with a Box-Behnken Design (BBD) was used to optimize extraction conditions. The optimal extraction parameters of PRG were as follows: extracting time 4 h, extraction temperature 77.3 °C and liquid-solid ratio 42.5 g/L. Furthermore, the data demonstrated that PRG exhibited antioxidant activities evidenced by reducing power to scavenge the DPPH, ABTS, hydroxyl radical and superoxide radical. PRG showed the activity of anti-cervical carcinoma cells Hela and Siha. In conclusion this study offered an efficient extraction method of wild Russula griseocarnosa polysaccharide, and the results suggested PRG had good antioxidant and inhibitory activities against cervical carcinoma cells, and PRG could be developed as a novel natural functional food.

Initial classification of pediatric hearing impairment using behavioral measures of early prelingual auditory development.

OBJECTIVE: Determine the sensitivity, specificity, and accuracy of pediatric hearing loss classification using behavioral evidence of early prelingual auditory development (EPLAD). Validate behavioral measures of EPLAD. DESIGN: EPLAD was assessed in a prospective sample of hearing-impaired children using the infant-toddler meaningful auditory integration scale (ITMAIS/MAIS). Hearing losses were classified using tone-burst auditory brainstem response (ABR) and ITMAIS/MAIS scores. This process was repeated in a second retrospective sample. STUDY SAMPLE: The prospective sample was comprised of 139 hearing-impaired children under five years of age. Approximately equal proportions of mild-moderate, severe, and profound losses were included. The second retrospective sample was comprised of case records for 144 hearing-impaired children meeting the same selection criteria. This sample contained more than 80% profound losses. RESULTS: EPLAD trajectories reached different asymptotes after two years of age, depending on the severity of hearing loss, allowing children over this age to be classified. The sensitivity of EPLAD classifications was over 90%; specificity was over 82%; and accuracy was over 88%. CONCLUSIONS: Behavioral evidence of EPLAD provides an initial means of classifying pediatric hearing losses which can facilitate initial treatment options prior to diagnostic evaluation with tone-burst ABR.

Psychometric properties of a Mandarin version of the tinnitus questionnaire.

OBJECTIVE: To develop a Mandarin version of the tinnitus questionnaire (MTQ) and determine the reliability and validity, and to assess whether it could be used clinically in the Chinese population. DESIGN: The MTQ, short-form (36) health survey, hospital anxiety and depression scale, Mandarin (Chinese) tinnitus handicap inventory, and visual analogue scale were completed by the participants. STUDY SAMPLE: We included 192 adults seeking treatment for primary or secondary tinnitus. RESULTS: Five factors, namely, emotional distress, auditory perceptual difficulties, cognitive distress, sleep disturbance, and intrusiveness, were extracted from the MTQ. Thirty-seven items were included. The MTQ had high test-retest reliability (Spearman correlation coefficients: 0.87-1.00). The MTQ and its subscales had good internal consistency and reliability (total α = 0.93, subscales α = 0.71-0.86). A single measure of severity can be acquired by summing the five subscale scores. The MTQ was significantly correlated with psychological distress and tinnitus-related handicap. CONCLUSION: Our results demonstrated that the MTQ is a reliable and valid measure of tinnitus-related psychopathological symptoms and could be used clinically to evaluate tinnitus-related psychological problems. Questionnaires designed to explore tinnitus-related depression and other symptoms not covered by the scope of the MTQ are needed.

Quantification of the effects of Mandarin dialect differences on the use of norm-referenced speech perception tests.

OBJECTIVE: Determine the effects of Chinese dialects on results for the Mandarin HINT recorded with a talker speaking Standard Mandarin (Putonghua). DESIGN: Normally-hearing subjects with different dialect exposure histories and usage preferences were administered the Mandarin HINT, and results were compared with published norms. Additional published measures of the intelligibility and mutual intelligibility of Chinese dialects were used to identify dialects for which Putonghua is highly intelligible. STUDY SAMPLE: One sample (N = 19) was exposed to a variety of dialects throughout China during childhood, and used Putonghua as adults. A second sample (N = 22) was exposed to Sichuanhua (the dialect found in Sichuan province) during childhood, and used Sichuanhua as adults. RESULTS: The average difference in SRTs for the Putonghua and Sichuanhua groups was 0.66 dB, with the Sichuanhua group's SRTs slightly higher. Means for neither group fell outside the confidence intervals for the norms. Putonghua is intelligible for 98% of Sichuanhua dialect users, and for over 90% of the users of two-thirds of the remaining Chinese regional dialects. CONCLUSIONS: Norm-referenced speech perception tests, such as the Mandarin HINT, can be used with speakers of Chinese regional dialects for whom Putonghua is highly intelligible. Small differences in dialect-specific norms are not clinically significant.

Metabolism of fungicide 2-allylphenol in Rhizoctonia cerealis.

2-Allylphenol is a biomimetic synthetic fungicide that mimics the compound ginkgol found in gingko fruit (Gingko biloba L.). This systemic fungicide can effectively suppress a wide range of plant diseases, including wheat sharp eyespot (Rhizoctonia cerealis). However, its degradation in environment after application is still unknown. To understand this fungicide degradation, major metabolites of 2-allylphenol in R. cerealis were examined. The parent and metabolites of 2-allylphenol were detected and quantified in the mycelia and liquid medium. Results showed that 2-allylphenol was metabolized and bio-transformed by R. cerealis, and four metabolites were found, including 2-(2-hydroxyphenyl) acetic acid (M1), 2-(2, 3-dihydroxypropyl) phenol (M2), 2-(2-hydroxypropyl)-phenol (M3) and 2-(3-hydroxypropyl)-phenol (M4). Based on the results, we propose that the biodegradation pathway is that 2-allylphenol is rapidly oxidized into metabolite M2 and hydrolyzed into M3 and M4, which formed M2, and carboxylation of M2 to 2-hydroxy-3-(2׳-hydroxyphenyl) propionic acid which undergo hydrolyzation and decarboxylation to form M1. 2-Allylphenol can be bio-transformed to new compounds by R. cerealis, suggesting the existence of microbe metabolic pathways for 2-allylphenol.

Effects of different speed-accuracy instructions on perception in psychology experiments: evidence from event-related potential and oscillation.

Introduction: In cognitive behavioral experiments, we often asked participants to make judgments within a deadline. However, the most common instruction of "do the task quickly and accurately" does not highlight the importance of the balance between being fast and accurate. Methods: Our research aimed to explore how instructions about speed or accuracy affect perceptual process, focus on event-related potentials (ERPs) and event-related oscillations (EROs) of two brain responses for visual stimuli, known as P1 and N1. Additionally, we compared the conventional analysis approach with principal component analysis (PCA) based methods to analyze P1 and N1 ERP amplitude and ERO power. Results: The results showed that individuals instructed to respond quickly had lower P1 amplitude and alpha ERO than those who prioritized accuracy, using the PCA-based approach. However, these two groups had no differences between groups in the N1 theta band using both methods. The traditional time-frequency analysis method could not detect any ERP or ERO distinctions between groups due to limitations in detecting specific components in time or frequency domains. That means PCA is effective in separating these components. Discussion: Our findings indicate that the instructions given regarding speed and accuracy impact perceptual process of subjects during cognitive behavioral experiments. We suggest that future researchers should choose their instructions carefully, considering the purpose of study.

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.

Prion protein E219K polymorphism: from the discovery of the KANNO blood group to interventions for human prion disease.

KANNO is a new human blood group that was recently discovered. The KANNO antigen shares the PRNP gene with the prion protein and the prion protein E219K polymorphism determines the presence or absence of the KANNO antigen and the development of anti-KANNO alloantibodies. These alloantibodies specifically react with prion proteins, which serve as substrates for conversion into pathological isoforms in some prion diseases and may serve as effective targets for resisting prion infection. These findings establish a potential link between the KANNO blood group and human prion disease via the prion protein E219K polymorphism. We reviewed the interesting correlation between the human PRNP gene's E219K polymorphism and the prion proteins it expresses, as well as human red blood cell antigens. Based on the immune serological principles of human blood cells, the prion protein E219K polymorphism may serve as a foundation for earlier molecular diagnosis and future drug development for prion diseases.

Tremella aurantialba polysaccharides alleviates ulcerative colitis in mice by improving intestinal barrier via modulating gut microbiota and inhibiting ferroptosis.

We aimed to investigate the effect of a polysaccharide from Tremella aurantialba on ulcerative colitis (UC), which targets ferroptosis in epithelial cells. TA 2-1 (127 kDa) was isolated from T. aurantialba and consisted of Man, Xyl, GlcA, Glc, Fuc and Rha with a molar ratio of 59.2: 23.2: 13.9: 1.6: 1.7: 0.4, exhibited a 1, 3-Man structure with branch chains of T-Xylp, 1,3-Xylp, 1,4-GlcAp, and T-Manp at its O-2 position. TA 2-1 (100 mg/mL) inhibited the cell viability of ferroptosis (19.8 %) in RLS3-induced Caco2 cells and significantly ameliorated symptoms in the colons of mice with dextran sodium sulfate (DSS)-induced UC. TA 2-1 remarkably repaired the intestinal barrier by upregulating claudin-1 and zonula occludens-1 levels. Further analysis found TA 2-1 significantly suppressed lipid peroxidation by regulating ferroptosis-related proteins in UC mice, suggesting that its protective effects are partially mediated by inhibiting ferroptosis. Further analysis of the gut microbiota and fecal microbiota transplantation revealed TA 2-1 might relieve UC symptoms or inhibit ferroptosis by modulating the gut microbiota's composition or metabolites. Results suggest the protective effects of TA 2-1 on the intestinal barrier by inhibiting ferroptosis of epithelial cells, at least by regulating the gut microbiota, highlighting the potential of TA 2-1 in UC treatment.

Development and Validation of a Nomogram for Predicting Acute Kidney Injury in Septic Patients.

Purpose: Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients. Patients and Methods: We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital. Results: 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value. Conclusion: The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.