Enhancing Lower Eyelid Suspension Outcomes Through Pre-surgical Facial Nerve Reanimation: A Comparative Study.

BACKGROUND: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension. METHODS: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness. RESULTS: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry. CONCLUSIONS: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparative efficacy of radical prostatectomy and radiotherapy in the treatment of high-risk prostate cancer.

BACKGROUND: Both radical prostatectomy and radiation therapy are effective in controlling the condition of patients with hormone-resistant prostate cancer (HRPCa). However, there is limited research on the prognosis and quality of life of HRPCa patients after different treatment modalities. OBJECTIVE: To explore the efficacy of radical prostatectomy (RP) and radiotherapy (RT), when treating high-risk prostate cancer (HRPCa). METHODS: Overall 103 HRPCa patients were included and were divided into RP group and RT group according to different treatment methods. The propensity score matching method (PSM) was used to balance the baseline data of the two groups and match 34 patients in each group. The prognosis, quality of life, and basic efficacy of patients were compared. RESULTS: After intervention, the disease-free survival rate of the RT group was higher than that of the RP group (79.41% vs. 55.88%, p= 0.038). Quality of life scores between the two treatment methods had no difference before intervention (p> 0.05), but higher in RT group than that of the RP group after intervention (p< 0.05). After treatment, there was no statistically significant difference in total effective rate of treatment between two groups (44.12% vs. 58.82%, p> 0.05), but the disease control rate was significantly higher in RT group (94.12% vs. 76.47%, p= 0.040). CONCLUSION: Radical radiotherapy is effective in the clinical treatment of HRPCa patients, with a higher disease-free survival rate and improved quality of life after treatment, and is worth promoting.

IL-17B alleviates the pathogenesis of systemic lupus erythematosus by inhibiting FASN-mediated differentiation of B cells.

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not clear. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center (GC) B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor (TLR) and interferon (IFN) pathways in B cells by downregulating the FASN-mediated lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study described the role of IL-17B in regulating B-cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.

MG53 inhibits ferroptosis by targeting the p53/SLC7A11/GPX4 pathway to alleviate doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an anthracycline medication that is commonly used to treat solid tumors. However, DOX has limited clinical efficacy due to known cardiotoxicity. Ferroptosis is involved in DOX-induced cardiotoxicity (DIC). Although mitsugumin-53 (MG53) has cardioprotective effects and is expected to attenuate myocardial ischemic injury, its ability to inhibit DOX-induced ferroptosis has not been extensively studied. This research aims to investigate the pathophysiological impact of MG53 on DOX induced ferroptosis. Here, MG53 levels were evaluated in relation to the extent of ferroptosis by establishing in vivo and in vitro DIC mouse models. Additionally, myocardial specific MG53 overexpressing mice were used to study the effect of MG53 on cardiac function in DIC mice. The study found that the MG53 expression decreased in DOX treated mouse hearts or cardiomyocytes. However, MG53-overexpressing improved cardiac function in the DIC model and effectively reduced myocardial ferroptosis by increasing solute carrier family 7 member 11 (SLC7A11) and Glutathione peroxidase 4 (GPX4) levels, which were decreased by DOX. Mechanistically, MG53 binds to tumor suppressor 53 (p53) to regulate its ubiquitination and degradation. Ferroptosis induced by DOX was prevented by either MG53 overexpression or p53 knockdown in cardiomyocytes. The modulation of the p53/SLC7A11/GPX4 pathway by overexpression of MG53 can alleviate DOX induced ferroptosis. The study indicates that MG53 can provide protection against DIC by increasing p53 ubiquitination. These results highlight the previously unidentified role of MG53 in inhibiting ferroptosis to prevent DIC.

A Comprehensive Analysis of LYAR in Colorectal Cancer: Prognostic Marker and Therapeutic Target.

Background: Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work aimed to investigate the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. Methods: We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. Results: LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. Conclusions: LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.

Electron spin resonance analysis of photoenzymatic catalysis.

This Perspective highlights recent research progress and prospects in elucidating the catalytic mechanism of photoenzymes using ESR (electron spin resonance) spectroscopy, which is emerging as a unique and crucial method for identifying radical intermediates, illustrating electron transfer events and the underlying mechanisms of photoenzymatic catalysis.

Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Facial recognition models for identifying genetic syndromes associated with pulmonary stenosis in children.

BACKGROUND: Williams-Beuren syndrome, Noonan syndrome, and Alagille syndrome are common types of genetic syndromes (GSs) characterized by distinct facial features, pulmonary stenosis, and delayed growth. In clinical practice, differentiating these three GSs remains a challenge. Facial gestalts serve as a diagnostic tool for recognizing Williams-Beuren syndrome, Noonan syndrome, and Alagille syndrome. Pretrained foundation models (PFMs) can be considered the foundation for small-scale tasks. By pretraining with a foundation model, we propose facial recognition models for identifying these syndromes. METHODS: A total of 3297 (n = 1666) facial photos were obtained from children diagnosed with Williams-Beuren syndrome (n = 174), Noonan syndrome (n = 235), and Alagille syndrome (n = 51), and from children without GSs (n = 1206). The photos were randomly divided into five subsets, with each syndrome and non-GS equally and randomly distributed in each subset. The proportion of the training set and the test set was 4:1. The ResNet-100 architecture was employed as the backbone model. By pretraining with a foundation model, we constructed two face recognition models: one utilizing the ArcFace loss function, and the other employing the CosFace loss function. Additionally, we developed two models using the same architecture and loss function but without pretraining. The accuracy, precision, recall, and F1 score of each model were evaluated. Finally, we compared the performance of the facial recognition models to that of five pediatricians. RESULTS: Among the four models, ResNet-100 with a PFM and CosFace loss function achieved the best accuracy (84.8%). Of the same loss function, the performance of the PFMs significantly improved (from 78.5% to 84.5% for the ArcFace loss function, and from 79.8% to 84.8% for the CosFace loss function). With and without the PFM, the performance of the CosFace loss function models was similar to that of the ArcFace loss function models (79.8% vs 78.5% without PFM; 84.8% vs 84.5% with PFM). Among the five pediatricians, the highest accuracy (0.700) was achieved by the senior-most pediatrician with genetics training. The accuracy and F1 scores of the pediatricians were generally lower than those of the models. CONCLUSIONS: A facial recognition-based model has the potential to improve the identification of three common GSs with pulmonary stenosis. PFMs might be valuable for building screening models for facial recognition. Key messages What is already known on this topic:  Early identification of genetic syndromes (GSs) is crucial for the management and prognosis of children with pulmonary stenosis (PS). Facial phenotyping with convolutional neural networks (CNNs) often requires large-scale training data, limiting its usefulness for GSs. What this study adds:  We successfully built multi-classification models based on face recognition using a CNN to accurately identify three common PS-associated GSs. ResNet-100 with a pretrained foundation model (PFM) and CosFace loss function achieved the best accuracy (84.8%). Pretrained with the foundation model, the performance of the models significantly improved, although the impact of the type of loss function appeared to be minimal. How this study might affect research, practice, or policy:  A facial recognition-based model has the potential to improve the identification of GSs in children with PS. The PFM might be valuable for building identification models for facial detection.

Effectiveness of Cognitive-Based Interventions on Psychological Distress in Adolescents With Physical Disabilities: A Systematic Review and Meta-Analysis.

Adolescents with physical disabilities experience common psychological distress that interacts with impaired physical function. While cognitive-based interventions have been implemented for adolescents with physical disabilities, their effects on enhancing psychological health remain uncertain. This systematic review aimed to synthesise the effects of cognitive-based interventions on the psychological distress of this population and identify optimal components for evidence-based interventions. Following the PRISMA guideline, nine databases were searched to identify eligible randomised controlled trials examining the effects of cognitive-based interventions for adolescents with physical disabilities from inception to October 2023. Data syntheses were performed using the R software, employing random-effects models. Twelve trials involving 1201 participants were identified. The pooled results revealed that cognitive-based interventions did not yield noticeable effects in reducing anxiety (g = -0.43 for postintervention; -0.14 for medium term; -0.37 for long term), depression (g = -0.05 for postintervention; -0.02 for medium term; -0.15 for long term) and stress levels (g = -0.15) over time. The secondary outcome (physical function) improved significantly in the long term compared to the control groups (g = 0.31). Furthermore, this review identified variations in the effectiveness of CBIs among different recipients, durations and modes of delivery. Given the limited number and overall low quality of identified studies for each outcome, conducting high-quality randomised controlled trials is recommended to validate the effectiveness of cognitive-based interventions in reducing psychological distress among adolescents with physical disabilities.

Pemphigoid diseases in patients with end-stage kidney diseases: pathogenesis and treatment.

Background: Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. Methods: A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Results: Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Conclusion: Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.

Targeting astrocytic TDAG8 with delayed CO2 postconditioning improves functional outcomes after controlled cortical impact injury in mice.

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.

Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis.

BACKGROUND: The growing consensus links exposure to fine particulate matter (PM2.5) with an increased risk of respiratory diseases. However, little is known about the additional effects of particulate matter on brainstem function in allergic rhinitis (AR). Furthermore, it is unknown to what extent the PM2.5-induced effects in the brainstem affect the inflammatory response in AR. This study aimed to determine the effects, mechanisms and consequences of brainstem neural activity altered by allergenic stimulation and PM2.5 exposure. METHODS: Using an AR model of ovalbumin (OVA) elicitation and whole-body PM2.5 exposure, the metabolic profile of the brainstem post-allergen stimulation was characterized through in vivo proton magnetic resonance imaging (1H-MRS). Then, the transient receptor potential vanilloid-1 (TRPV1) neuronal expression and sensitivity in the trigeminal nerve in AR were investigated. The link between TRPV1 expression and brainstem differential metabolites was also determined. Finally, we evaluated the mediating effects of brainstem metabolites and the consequences in the brain-spleen axis in the inflammatory response of AR. RESULTS: Exposure to allergens and PM2.5 led to changes in the metabolic profiles of the brainstem, particularly affecting levels of glutamine (Gln) and glutamate (Glu). This exposure also increased the expression and sensitivity of TRPV1+ neurons in the trigeminal nerve, with the levels of TRPV1 expression closely linked to the brainstem metabolism of Glu and Gln. Moreover, allergens increased the activity of p38, while PM2.5 led to the phosphorylation of p38 and ERK, resulting in the upregulation of TRPV1 expression. The brainstem metabolites Glu and Gln were found to partially mediate the impact of TRPV1 on AR inflammation, which was supported by the presence of pro-inflammatory changes in the brain-spleen axis. CONCLUSION: Brainstem metabolites are altered under allergen stimulation and additional PM2.5 exposure in AR via sensitization of the trigeminal nerve, which exacerbates the inflammatory response via the brain-splenic axis.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

Research on ultrasound-based radiomics: a bibliometric analysis.

Background: A large number of studies related to ultrasound-based radiomics have been published in recent years; however, a systematic bibliometric analysis of this topic has not yet been conducted. In this study, we attempted to identify the hotspots and frontiers in ultrasound-based radiomics through bibliometrics and to systematically characterize the overall framework and characteristics of studies through mapping and visualization. Methods: A literature search was carried out in Web of Science Core Collection (WoSCC) database from January 2016 to December 2023 according to a predetermined search formula. Bibliometric analysis and visualization of the results were performed using CiteSpace, VOSviewer, R, and other platforms. Results: Ultimately, 466 eligible papers were included in the study. Publication trend analysis showed that the annual publication trend of journals in ultrasound-based radiomics could be divided into three phases: there were no more than five documents published in this field in any year before 2018, a small yearly increase in the number of annual publications occurred between 2018 and 2022, and a high, stable number of publications appeared after 2022. In the analysis of publication sources, China was found to be the main contributor, with a much higher number of publications than other countries, and was followed by the United States and Italy. Frontiers in Oncology was the journal with the highest number of papers in this field, publishing 60 articles. Among the academic institutions, Fudan University, Sun Yat-sen University, and the Chinese Academy of Sciences ranked as the top three in terms of the number of documents. In the analysis of authors and cocited authors, the author with the most publications was Yuanyuan Wang, who has published 19 articles in 8 years, while Philippe Lambin was the most cited author, with 233 citations. Visualization of the results from the cocitation analysis of the literature revealed a strong centrality of the subject terms papillary thyroid cancer, biological behavior, potential biomarkers, and comparative assessment, which may be the main focal points of research in this subject. Based on the findings of the keyword analysis and cluster analysis, the keywords can be categorized into two major groups: (I) technological innovations that enable the construction of radiomics models such as machine learning and deep learning and (II) applications of predictive models to support clinical decision-making in certain diseases, such as papillary thyroid cancer, hepatocellular carcinoma (HCC), and breast cancer. Conclusions: Ultrasound-based radiomics has received widespread attention in the medical field and has been gradually been applied in clinical research. Radiomics, a relatively late development in medical technology, has made substantial contributions to the diagnosis, prediction, and prognostic evaluation of diseases. Additionally, the coupling of artificial intelligence techniques with ultrasound imaging has yielded a number of promising tools that facilitate clinical decision-making and enable the practice of precision medicine. Finally, the development of ultrasound-based radiomics requires multidisciplinary cooperation and joint efforts from the field biomedicine, information technology, statistics, and clinical medicine.

Recent symptomatic Omicron infection reduced COVID-19 pneumonia risk during reinfection: A computed tomography-based cohort study.

OBJECTIVES: SARS-CoV-2 infection could cause persistent lung injury or indicate potential genetic susceptibilities. Although infection-elicited hybrid immunity could protect against severe COVID-19, it remains unknown whether recent infection could reduce pneumonia risk during reinfection due to insufficient viral and chest computed tomography (CT) screening. METHODS: A total of 15,598 patients, 96% fully vaccinated and 52% boosted, from Xiangyang, China, who had symptomatic COVID-19 and chest CT scans during the first Omicron BF.7 wave in December 2022 to January 2023, were followed through the second Omicron XBB.1.5 wave between May and August 2023. A total of 17,968 second-wave patients with COVID-19 with chest CT scans but without previous symptomatic COVID-19 were enrolled as first-time infection controls. RESULTS: A total of 19.6% (3,061 of 15,598) first-wave patients were diagnosed with pneumonia. Among second-wave reinfected patients, only 0.2% (four of 2202) developed pneumonia, which was lower than the 1.7% (311 of 17,968) pneumonia prevalence among the second-wave first-time patients, with an adjusted relative risk of 0.11 (95% confidence interval: 0.04-0.29). A total of 1.3% (40 of 3,039) first-wave pneumonia survivors showed residual abnormal patterns in follow-up CT scans within 8 months after pneumonia diagnosis. CONCLUSIONS: In a highly vaccinated population, previous symptomatic Omicron infection within 8 months reduced pneumonia risk during reinfection. Uninfected individuals might need up-to-date vaccination to reduce pneumonia risk.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Galectin-3 contributes to pathogenesis of IgA nephropathy.

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis, and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.

Reg2 treatment is protective but the induced Reg2 autoantibody is destructive to the islets in NOD mice.

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates ß-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased ß-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet ß-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.