Novel chimney balloon technique to safeguard cerebral blood flow during total endovascular aortic arch repair.

During endovascular total aortic arch repair by in situ fenestration, extra procedures are needed to sustain cerebral blood flow when targeting all three supra-aortic branches. Recently, our group successfully interposed a chimney balloon between the greater curvature of the aortic arch and an aortic stent to safeguard cerebral blood flow during total endovascular aortic arch repair.

Comprehensive analysis of cellular senescence and immune microenvironment in papillary thyroid carcinoma.

Senescence-induced therapy was previously considered as an effective treatment for tumors, and cellular senescence was initially regarded as an effective mechanism against cancer. However, whether cell senescence-related genes can be used to predict the prognosis of papillary thyroid carcinoma (PTC) and immunotherapy remains unclear. We developed and validated a cell senescence-related signature (CSRS) by analyzing the gene expression of 278 genes related to cellular senescence in 738 patients with PTC. Additionally, further analysis showed that CSRS was a reliable predictor of patient outcomes in combination with immune checkpoint expression and drug susceptibility, and patients with high risk scores may benefit from immunotherapy. The findings of this study demonstrate that CSRS serves as an immunotherapeutic response and prognosis biomarker affecting the tumor immune microenvironment of PTC.

High-intensity aerobic exercise training improves exercise capacity, dyspnea, and fatigue in patients with severe asthma using triple inhaler.

Objectives: Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma. Materials and Methods: Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO2). Results: Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters. Conclusion: HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters.

Clinical implications of diverse calcification patterns in endovascular therapy for femoral-popliteal arterial occlusive disease.

OBJECTIVE: The aim of this study was to investigate whether intimal arterial calcification (IAC) and medial arterial calcification (MAC) are correlated with the various clinical outcomes following endovascular therapy (EVT) for peripheral arterial disease (PAD). METHODS: This single-center retrospective study comprised 154 consecutively hospitalized individuals with PAD who underwent EVT for de novo femoral-popliteal calcific lesions from January 2016 to July 2021. The predominant calcification patterns of IAC and MAC were assessed using a semi-quantitative computed tomography scoring system. The Kaplan-Meier method and Cox regression were conducted to evaluate the correlations between calcification patterns and medium- to long-term outcomes. RESULTS: The distribution of calcification patterns was as follows: IAC in 111 patients (72%) and MAC in 43 patients (28%). No remarkable variation was noted between the IAC and MAC groups regarding age (P = .84) and gender (P = .23). The MAC group indicated lower rates of 4-year primary patency, assisted primary patency, secondary patency, and amputation-free survival (AFS) compared with the IAC group (24% ± 7% vs 40% ± 6%; P = .003; 30% ± 8% vs 51% ± 6%; P = .001; 51% ± 8% vs 65% ± 5%; P = .004; and 43% ± 9% vs 76% ± 5%; P < .001, respectively). There was no significant difference in the rate of freedom from clinically driven target lesion revascularization between the MAC and IAC groups (63% ± 10% vs 73% ± 5%; P = .26). Stepwise multivariable Cox regression analysis demonstrated that MAC was associated with poor patency (hazard ratio, 1.81; 95% confidence interval, 1.12-2.93; P = .016) and AFS (hazard ratio, 2.80; 95% confidence interval, 1.52-5.16; P = .001). CONCLUSIONS: Compared with IAC, MAC is independently associated with lower medium- to long-term patency and AFS after EVT for de novo femoral-popliteal occlusive lesions.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

CD6 triggers actomyosin cytoskeleton remodeling after binding to its receptor complex.

The T cell marker CD6 regulates both T cells and target cells during inflammatory responses by interacting with its receptors. However, only a few receptors binding to the extracellular domains of CD6 have been identified, and cellular events induced by CD6 engagement with its receptors in target cells remain poorly understood. In this study, we identified CD44 as a novel CD6 receptor by proximity labeling and confirmed the new CD6-CD44 interaction by biochemical and biophysical approaches. CD44 and the other 2 known CD6 receptors, CD166 and CDCP1, were distributed diffusely on resting retinal pigment epithelium (RPE) cells but clustered together to form a receptor complex upon CD6 binding. CD6 stimulation induced dramatic remodeling of the actomyosin cytoskeleton in RPE cells mediated by activation of RhoA, and Rho-associated kinase signaling, resulting in increased myosin II phosphorylation. Such actomyosin activation triggered the disassembly of tight junctions responsible for RPE barrier integrity in a process that required all components of the tripartite CD6 receptor complex. These data provided new insights into the mechanisms by which CD6 mediates T cell-driven disruption of tissue barriers during inflammation.

Traumatic Aortic Dissection as a Unique Clinical Entity: A Single-Center Retrospective Study.

BACKGROUND: This study aimed to compare the clinical characteristics, treatment approaches, and outcomes of the Stanford Type B traumatic aortic dissection (TAD) with non-traumatic aortic dissection (NTAD), and assess better management for TAD. METHODS: We retrospectively analyzed patients who underwent thoracic endovascular aortic repair for Stanford type B aortic dissection at The First Hospital of China Medical University between 2014 and 2022. The patients were divided into TAD and NTAD groups based on whether they had a history of acute trauma. This study ultimately included 65 patients with TAD and 288 with NTAD. We assessed and compared the baseline characteristics, laboratory indicators, imaging features, surgical procedures, and follow-up results between the groups. RESULTS: The TAD group was younger compared to the NTAD group (50.00 [IQR40.00-59.00] vs. 55.00 [IQR 47.00-61.00] years, p = 0.020). A lower percentage of the TAD group had a history of hypertension (20% vs. 71.18%, p < 0.001). The length of aortic dissection was shorter in the TAD group compared to the NTAD group (30.00 [IQR 22.00-40.00] vs. 344.00 [IQR 237.25-400.00] mm, p < 0.001). All patients with TAD underwent TEVAR following the same strategy as NTAD. The mean preoperative duration was 7.00 (IQR 2.00-14.00) days in the TAD group and 11.00 (IQR 8.00-15.00) days in the NTAD group (p < 0.001). TAD showed fewer complications after TEVAR in mid-to-long-term follow-up. CONCLUSIONS: TAD is distinct from NTAD. TAD typically presents with more localized lesions than NTAD, and the patients experience a shorter preoperative duration and a better mid-to-long-term outcome.

Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise.

Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skipping events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL.

Clinical progression of asynchronous cutaneous lesions in a patient with locally acquired mpox infection.

We present one of the earliest domestic mpox cases in Taiwan, highlighting the asynchronous and atypical progression of cutaneous lesions which could pose significant diagnostic challenges for clinicians.

The Influence of Diabetes Mellitus on Mortality of Patients After Lower Extremity Amputation: A Systematic Review and Meta-analysis.

OBJECTIVE: The influence of diabetes mellitus (DM) on mortality following lower extremity amputation (LEA) remains controversial. This systematic review and meta-analysis aimed to determine the influence of DM on long-term mortality (LTM) and short-term mortality (STM) after amputation. MATERIALS AND METHODS: The Medline, the Cochrane library, and Embase databases were searched. The primary and secondary outcomes were LTM and STM following amputation. One-year and 30-day all-cause mortality after amputation were considered as LTM and STM, respectively. A random-effects model was utilized to pool results. To evaluate the stability of results, subgroup analyses and sensitivity analyses were conducted. RESULTS: Twenty-three cohort studies with a total of 58,219 patients were included, among which 31,750 (54.5%) patients had DM. The mean score of included studies evaluated by Newcastle-Ottawa Scale was 7.65, indicating moderate to high quality. The pooled results showed no significant difference in 1-year LTM (risk ratio [RR], 0.96; 95% CI 0.86-1.07) after amputation. However, 3-year (RR, 1.22; 95% CI 1.01-1.47) and 5-year (RR, 1.18; 95% CI 1.07-1.31) LTMs of DM patients were obviously higher than that of NDM (non-diabetes mellitus) patients. The STM of the DM group was significantly lower than the NDM group (RR, 0.80; 95% CI 0.64-0.98). CONCLUSIONS: The current study revealed that DM patients had an obvious lower STM following LEA, but the risk of DM on LTM after amputation was gradually increased with time. More attention should be paid to the long-term survival of DM patients after LEA.

Correlation between clinical characteristics and tinnitus severity in tinnitus patients of different sexes: an analytic retrospective study.

PURPOSE: This study aimed to explore whether sex is influences tinnitus severity and whether the risk factors for tinnitus severity are the same in tinnitus patients of different sexes. METHODS: This was a retrospective study of data from 1427 patients complaining of tinnitus in a local hospital otolaryngology clinic from November 2019 to January 2022. All patients were interviewed and assessed by otoscopy, pure-tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS), and tinnitus refinement test. RESULTS: THI values were higher in females than in males (P = 0.00). Types of tinnitus sounds (OR 0.667, P = 0.000) and degree of hearing loss (OR 1.318, P = 0.000) were risk factors for tinnitus severity in males. Types of tinnitus sounds (OR 0.789, P = 0.005), sensation level (OR 1.023, P = 0.037), tinnitus types (OR 1.163, P = 0.041), tinnitus location (OR 1.198, P = 0.026), and the degree of hearing loss (OR 1.303, P = 0.000) were risk factors for tinnitus severity in females. Sex was an influencing factor for tinnitus severity. There were different risk factors for the tinnitus severity in different sexes. CONCLUSION: The risk factors for tinnitus severity differed according to sex in tinnitus patients, and the risk factors for tinnitus severity were greater in women than in men. These findings add to the literature on sex differences in tinnitus and suggest that medical and psychological screening of affected individuals and customized tinnitus treatment for each individual with tinnitus are needed. TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).

Development of an audiological assessment and diagnostic model for high occupational noise exposure.

PURPOSE: To explore the diagnostic auditory indicators of high noise exposure and combine them into a diagnostic model of high noise exposure and possible development of hidden hearing loss (HHL). METHODS: We recruited 101 young adult subjects and divided them according to noise exposure history into high-risk and low-risk groups. All subjects completed demographic characteristic collection (including age, noise exposure, self-reported hearing status, and headset use) and related hearing examination. RESULTS: The 8 kHz (P = 0.039) and 10 kHz (P = 0.005) distortion product otoacoustic emission amplitudes (DPOAE) (DPs) in the high-risk group were lower than those in the low-risk group. The amplitudes of the summating potential (SP) (P = 0.017) and action potential (AP) (P = 0.012) of the electrocochleography (ECochG) in the high-risk group were smaller than those in the low-risk group. The auditory brainstem response (ABR) wave III amplitude in the high-risk group was higher than that in the low-risk group. When SNR = - 7.5 dB (P = 0.030) and - 5 dB (P = 0.000), the high-risk group had a lower speech discrimination score than that of the low-risk group. The 10 kHz DPOAE DP, ABR wave III amplitude and speech discrimination score under noise with SNR = - 5 dB were combined to construct a combination diagnostic indicator. The area under the ROC curve was 0.804 (95% CI 0.713-0.876), the sensitivity was 80.39%, and the specificity was 68.00%. CONCLUSIONS: We expect that high noise exposure can be detected early with this combined diagnostic indicator to prevent HHL or sensorineural hearing loss (SNHL). TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057989, 2022/3/25.

Circular RNAs expression profiles and bioinformatics analysis in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) has long been considered the most challenging chronic lung disease for neonatologists and researchers due to its complex pathological mechanisms and difficulty in prediction. Growing evidence indicates that BPD is associated with the dysregulation of circular RNAs (circRNAs). Therefore, we aimed to explore the expression profiles of circRNAs and investigate the underlying molecular network associated with BPD. METHODS: Peripheral blood was collected from very-low-birth-weight (VLBW) infants at 5-8 days of life to extract PBMCs. Microarray analysis and qRT-PCR tests were performed to determine the differentially expressed circRNAs (DEcircRNAs) between BPD and non-BPD VLBW infants. Simultaneous analysis of GSE32472 was conducted to obtain differentially expressed mRNAs (DEmRNA) from BPD infants. The miRNAs were predicted by DEcircRNAs and DEmRNAs of upregulated, respectively, and then screened for overlapping ones. GO and KEGG analysis was performed following construction of the competing endogenous RNA regulatory network (ceRNA) for further investigation. RESULTS: A total of 65 circRNAs (52 upregulated and 13 downregulated) were identified as DEcircRNAs between the two groups (FC >2.0 and p.adj <0.05). As a result, the ceRNA network was constructed based on three upregulated DEcircRNAs validated by qRT-PCR (hsa_circ_0007054, hsa_circ_0057950, and hsa_circ_0120151). Bioinformatics analysis indicated these DEcircRNAs participated in response to stimulus, IL-1 receptor activation, neutrophil activation, and metabolic pathways. CONCLUSIONS: In VLBW infants with a high risk for developing BPD, the circRNA expression profiles in PBMCs were significantly altered in the early post-birth period, suggesting immune dysregulation caused by infection and inflammatory response already existed.

Clinical Characteristics and Risk Factors of Noninfectious Fever after Thoracic Endovascular Aortic Repair of Acute Type B Aortic Dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is gradually becoming a first-line treatment of complicated acute type B aortic dissection (ATBAD). Interestingly, according to years of experience in the treatment of ATBAD, we found that patients with ATBAD often had unexplained noninfectious fever after TEVAR. This study aims to explore its clinical characteristics and independent risk factors. METHODS: From January 2016 to September 2021, 211 consecutive patients treated electively by TEVAR for ATBAD were included. The entry tears in all patients originated in the distal to the left subclavian artery (LSA). All patients were diagnosed with ATBAD for the first time. The definition of fever in this study was that the body temperature of patients after TEVAR exceeds 38°C. RESULTS: A total of 211 patients (53.62 ± 11.34 years, 81% men) were included in the analysis. To compare patients who did and did not have post-TEVAR fever, they were respectively classified as the fever group and the nonfever group. Fever was diagnosed in 115 (55%) patients. Preoperatively, statistical differences were recorded in age (P = 0.023) and red blood cell (P = 0.037). Age <60 years [odds ratio (OR) 2.194, 95% confidence interval (CI) 1.147-4.196, P = 0.018] and duration of the operation >3 hr (OR 3.586, 95% CI 1.133-11.350, P = 0.03) were positively associated with fever. In the comparison of preoperative and postoperative experimental data, the changes in white blood cell (P = 0.046) and platelet (P = 0.007) of the 2 groups were significantly different. Hospital stay (P = 0.009) and postoperative hospital stay (P < 0.001) in the fever group were significantly prolonged. There was no difference in survival in the mid- and long-term follow-up between the 2 groups. CONCLUSIONS: Noninfectious fever occurs in more than half of the patients after TEVAR (115/211, 54.5%). Patients in the fever group are younger. Age <60 years and duration of the operation >3 hr are independent risk factors for noninfectious fever in patients with ATBAD after TEVAR fever. Noninfectious fever after TEVAR may lead to prolonged hospital stay. However, it did not affect mid- and long-term prognosis.

The effect and mechanism of Xihuang pill inhibits the formation of vasculogenic mimicry in human glioblastoma cells by down-regulating HIF-1α/VEGFA/VEGFR2 signaling pathway / 药学学报

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis.

Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer-1 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer-1 exerted its protective effects by scavenging of ROS and inhibition of TfR1-mediated ferroptosis and P53-AIFM2 signaling pathway-mediated apoptosis. Our findings suggest that Fer-1 is a promising drug for treating NIHL because of its ability to inhibit noise-induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.

Identifying Hub Genes and Immune Cell Infiltration for the Progression of Carotid Atherosclerotic Plaques in the Context of Predictive and Preventive Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.

Emerging evidence shows that carotid atherosclerosis is related to the activation of immune-related pathways and inflammatory cell infiltration. However, the immune-linked pathways that helped in the advancement of the carotid atherosclerotic plaque and the association of such plaques with the infiltration status of the body's immune cells still unclear. Here, the expression profiles of the genes expressed during the progression of the carotid atherosclerotic plaques were retrieved from the Gene Expression Omnibus database and 178 differentially expressed genes were examined. The Weighted Gene Coexpression Network Analysis technique identified one of the brown modules showed the greatest correlation with carotid atherosclerotic plaques. In total, 66 intersecting genes could be detected after combining the DEGs. LASSO regression analysis was subsequently performed to obtain five hub genes as potential biomarkers for carotid atherosclerotic plaques. The functional analysis emphasized the vital roles played by the inflammation- and immune system-related pathways in this disease. The immune cell infiltration results highlighted the significant correlation among the CD4+ T cells, B cells, macrophages, and CD8+ T cells. Thereafter, the gene expression levels and the diagnostic values related to every hub gene were further validated. The above results indicated that macrophages, B cells, CD4+ T cells, and CD8 + T cells were closely related to the formation of the advanced-stage carotid atherosclerotic plaques. Based on the results, it could be hypothesized that the expression of hub genes (C3AR1, SLAMF8, TMEM176A, FERMT3, and GIMAP4) assisted in the advancement of the early-stage to advanced-stage carotid atherosclerotic plaque through immune-related signaling pathways. This may help to provide novel strategies for the treatment of carotid plaque in the context of predictive, preventive, and personalized medicine.

Systemic steroid administration combined with intratympanic steroid injection in the treatment of a unilateral sudden hearing loss prognosis prediction model: A retrospective observational study.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency ear disease that is referred to as a sensorineural hearing loss of at least 30 dB in three sequential frequencies and occurs over a period of < 72 h. Because of its etiology, pathogenesis, and prognostic factors, the current treatment methods are not ideal. Previous studies have developed prognostic models to predict hearing recovery from ISSNHL, but few studies have incorporated serum biochemical indicators into previous models. The aim of this study was to explore the factors influencing the ISSNHL prognosis of combination therapy (combined intratympanic and systemic use of steroids, CT), among the patient population data, the serum biochemical indicators before the treatment, and the clinical features of ISSNHL. The new prediction model was developed through these factors. From November 2015 to April 2022, 430 patients who underwent CT at the Department of Otorhinolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University for ISSNHL, were reviewed retrospectively. We found significant differences in age (P = 0.018), glucose (P = 0.035), white blood cell (WBC) (P = 0.021), vertigo (P = 0.000) and type (P = 0.000) with different therapeutic efficacies. Multivariate logistic regression analysis showed that age (OR = 0.715, P = 0.023), WBC (OR = 0.527, P = 0.01), platelet to lymphocyte ratio (PLR) (OR = 0.995, P = 0.038), vertigo (OR = 0.48, P = 0.004), course (time from onset to treatment) (OR = 0.681, P = 0.016) and type (OR = 0.409, P = 0.000) were independent risk factors for ISSNHL prognosis. Based on independent risk factors, a predictive model and nomogram were developed to predict hearing outcomes in ISSNHL patients. The area under the curve (AUC) value of the model developed in this study was 0.773 (95% CI = 0.730-0.812), which has a certain predictive ability. The calibration curve indicated good consistency between the actual diagnosed therapeutic effectiveness and the predicted probability. The model and nomogram can predict the hearing prognosis of ISSNHL patients treated with CT and can provide help for medical staff to make the best clinical decision. This study has been registered with the registration number ChiCTR2200061379.

CDCP1 regulates retinal pigmented epithelial barrier integrity for the development of experimental autoimmune uveitis.

Cub domain-containing protein 1 (CDCP1) is a protein that is highly expressed on the surface of many cancer cells. However, its distribution in normal tissues and its potential roles in nontumor cells are poorly understood. We found that CDCP1 is present on both human and mouse retinal pigment epithelial (RPE) cells. CDCP1-KO mice developed attenuated retinal inflammation in a passive model of autoimmune uveitis, with disrupted tight junctions and infiltrating T cells detected in RPE flat mounts from WT but not CDCP1-KO mice during EAU development. Mechanistically, we discovered that CDCP1 on RPE cells was upregulated by IFN-γ in vitro and after EAU induction in vivo. CD6 stimulation induced increased RPE barrier permeability of WT but not CDCP1-knockdown (CDCP1-KD) RPE cells, and activated T cells migrated through WT RPE monolayers more efficiently than the CDCP1-KD RPE monolayers. In addition, CD6 stimulation of WT but not the CDCP1-KD RPE cells induced massive stress fiber formation and focal adhesion disruption to reduce cell barrier tight junctions. These data suggest that CDCP1 on RPE cells interacts with CD6 on T cells to induce RPE cytoskeleton remodeling and focal adhesion disruption, which open up the tight junctions to facilitate T cell infiltration for the development of uveitis.