Clinical Value Research Articles

Evaluating the effectiveness of handheld ultrasound in primary blast lung injury: a comprehensive study

The incidence of blast injuries has been rising globally, particularly affecting the lungs due to their vulnerability. Primary blast lung injury (PBLI) is associated with high morbidity and mortality rates, while early diagnostic methods are limited. With advancements in medical technology, and portable handheld ultrasound devices, the efficacy of ultrasound in detecting occult lung injuries early remains unclear. This study evaluates the effectiveness of immediate lung ultrasound in diagnosing PBLI. The study involved 25 healthy male Bama mini-pigs subjected to BST-I-type biological shock wave tubes. The pigs were randomly assigned to non-injured and injured groups with driving pressures of 4.0 MPa, 4.5 MPa, and 4.8 MPa. Four PBLI models were created: no injury, minor, moderate, serious and severe. Immediate lung ultrasound following the BLUE-PLUS protocol and arterial blood gas analysis were conducted pre-injury and 0.5 h, 3 h, 6 h, 12 h, and 24 h post-injury, respectively. The study analyzed lung ultrasound score differences and their correlations with lung function parameters, using ROC analysis to determine early diagnostic standards and mortality prediction efficacy. The study found that in cases of moderate and severe PBLI, lung ultrasound scores and AaDO2 significantly increased at 0.5 h post-injury, while PaO2 decreased. There was good consistency between left and right lung ultrasound results at all times. Lung ultrasound scores were significantly correlated with PaO2 and AaDO2 but not with PaCO2. The scores accurately predicted injury severity at various time points within 24 h post-injury, and the 0.5 h lung ultrasound score predicted 24 h mortality with 95.8% efficiency. PBLI exhibits hidden severity, necessitating improved early diagnostics. Immediate lung ultrasound provides effective differentiation for moderate and severe PBLI at multiple time points within 24 h post-injury, is easy to implement, and offers effective mortality risk prediction as early as 0.5 h post-injury. These findings underscore lung ultrasound’s significant clinical application value in pre-hospital early treatment settings for PBLI.

Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation

BackgroundLow-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood.MethodsThis study comprehensively analyzed several mainstream bioinformatics databases to explore the expression, diagnostic efficacy, clinical pathological features, immune infiltration, prognostic value, and biological functions of NCOA4 in LGG. Immunohistochemistry experiments were conducted using LGG tissue samples collected from our hospital to validate the bioinformatics analysis results.ResultsNCOA4 expression was significantly elevated in LGG (p < 0.05), with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.973, suggesting it as a potential diagnostic marker. High NCOA4 expression was associated with younger age (21–40 years), lower malignancy (oligodendroglioma), and better prognosis (IDHmut-non-codel and IDHmut-codel subtypes) (all p < 0.05) in LGG. Kaplan-Meier survival curves from three databases showed that high NCOA4-expressing LGG patients had better prognosis (all p < 0.05). NCOA4 correlated weakly with B cells, CD8 + T cells, macrophages, and dendritic cells infiltration (all with correlation coefficients r < 0.3, and p < 0.05) in LGG. Multivariate Cox regression identified NCOA4, age, CD8 T cells, and macrophages as LGG independent prognostic factors (all p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that NCOA4’s primary function in LGG is related to autophagy processes (all p < 0.05).ConclusionOur findings suggest that NCOA4 could be a potential prognostic marker and therapeutic target in LGG.

Clinical value of miR-200b in diagnosis and prognosis of childhood pneumonia

BackgroundChildhood pneumonia (CP) is a common respiratory infectious disease in children with high morbidity and mortality. However, differential changes in miRNAs may interact with the regulation of CP. The aim of this paper was to discuss the miR-200b expression in CP and its diagnostic and prognostic value.MethodsRT-qPCR was used to measure the miR-200b expression in venous blood. ROC curve was adopted to assess the diagnostic ability of miR-200b in children with CP. Logistic analysis was adopted to study the risk factors are related to CP. Kaplan-Meier was employed to analyze the prognostic ability of miR-200b in CP. Transfection of MRC-5 cells in vitro was used to verify the impact of miR-200b on cell proliferation and apoptosis.ResultsThe expression of miR-200b in serum of CP children was upregulated. ROC analysis prompted that upregulation of miR-200b could be effective in distinguishing between CP and healthy children. Compared with the good prognosis group, miR-200b expression was elevated in the poor prognosis group. Kaplan-Meier reminded that high expression of miR-200b led to a poor prognosis in CP. Cells experiments demonstrated that transfection with miR-200b inhibitor encouraged cell proliferation and inhibited apoptosis, whereas transfection with miR-200b mimic had the contrary result.ConclusionsmiR-200b had high diagnostic and prognostic value for children with CP and may become a biomarker for clinical diagnosis and prognosis.Clinical trial numberNot applicable.

Safety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.

The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers. The results confirmed that KJ103 rapidly reduced IgG and maintained plasma IgG at low levels for one week. Dose of KJ103 ranging from 0.01 to 0.40 mg/kg had a favorable safety and tolerability profile across diverse ethnic and gender groups. KJ103 demonstrated a lower incidence of pre-existing anti-drug antibodies (ADAs) compared to currently approved human IgG degrading enzyme Imlifidase, with most induced ADAs predominantly reverting to baseline six months after administration. These properties are ideal for the management of immune disorders, rejection responses, and immunotherapies where pre-existing antibodies can reduce efficacy. Furthermore, we tested AAV2 neutralizing antibodies to confirm the potential utility of KJ103 in enhancing gene therapy.

Exosomes in Autoimmune Diseases: A Review of Mechanisms and Diagnostic Applications.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation. Recent advancements in exosome isolation techniques and their molecular characterization have paved the way for exploring their clinical potential as biomarkers and therapeutic targets. This review focuses on the mechanisms by which exosomes influence autoimmune disease development and their potential clinical applications, particularly in diagnosis. The role of exosomes in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS), is discussed in relation to their involvements in antigen presentation, T-cell activation, and the induction of inflammatory pathways. Additionally, exosome-based biomarkers offer promising non-invasive diagnostic tools for early diagnostic, disease monitoring, and therapeutic response assessment. However, challenges such as standardization of exosome isolation protocols and validation of their clinical significance remain. This review highlights the potential of exosomes as both diagnostic biomarkers and therapeutic targets in autoimmune diseases, emphasizing the need for further research to overcome current limitations and fully harness their clinical value.

CircDNA2-Educated YTHDF2 Phase Separation Promotes PM2.5-Induced Malignant Transformation Through the Blunting of GADD45A Expression.

Substantial epidemiological evidence suggests a significant correlation between particulate matter 2.5 (PM2.5) and lung cancer. However, the mechanism underlying this association needs to be further elucidated. Circular RNAs (circRNAs) have emerged as an important topic in the field of epigenetics and are involved in various cancers. This study aimed to explore the molecular basis of PM2.5-induced lung cancer from an epigenetic perspective and identify potential biomarkers. Initially, the construction of a chronic PM2.5 exposure model confirmed that PM2.5 exposure promoted the malignant transformation of human bronchial epithelial (HBE) cells. Mechanistically, abnormally upregulated circDNA2 inhibited the tumor suppressor gene growth arrest and DNA damage 45 alpha (GADD45A) mRNA in an N6-methyladenosine (m6A)-dependent manner, mediated by YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) after PM2.5 exposure. Further analyses revealed that circDNA2 can specifically bind to the YTHDF2 LC domain to promote YTHDF2 protein liquid-liquid phase separation (LLPS), providing sufficient evidence linking LLPS and particulate pollutant-induced tumorigenesis. In conclusion, this study provides new insights into the role of circDNA2 in PM2.5-induced lung cancer and confirms its clinical value as a potential prognostic biomarker for lung cancer.

The application of a clinical-multimodal ultrasound radiomics model for predicting cervical lymph node metastasis of thyroid papillary carcinoma

BackgroundPTC (papillary thyroid cancer) is a lymphotropic malignancy associated with cervical lymph node metastasis (CLNM, including central and lateral LNM), which compromises the effect of treatment and prognosis of patients. Accurate preoperative identification will provide valuable reference information for the formulation of diagnostic and treatment strategies. The aim of this study was to develop and validate a clinical-multimodal ultrasound radiomics model for predicting CLNM of PTC.MethodsOne hundred sixty-four patients with PTC who underwent treatment at our hospital between March 2016 and December 2021 were included in this study. The patients were grouped into a training cohort (n=115) and a validation cohort (n=49). Radiomic features were extracted from the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) and strain elastography-ultrasound (SE-US) images of patients with PTC. Multivariate logistic regression analysis was used to identify the independent risk factors. FAE software was used for radiomic feature extraction and the construction of different prediction models. The diagnostic performance of each model was evaluated and compared in terms of the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value (NPV) and positive predictive value (PPV). RStudio software was used to develop the decision curve and assess the clinical value of the prediction model.ResultsThe clinical-multimodal ultrasound radiomics model developed in this study can successfully detect CLNM in PTC patients. A total of 3720 radiomic features (930 features per modality) were extracted from the ROIs of the multimodal images, and 15 representative features were ultimately screened. The combined model showed the best prediction performance in both the training and validation cohorts, with AUCs of 0.957 (95% CI: 0.918–0.987) and 0.932 (95% CI: 0.822–0.984), respectively. Decision curve analysis revealed that the combined model was superior to the other models.ConclusionThe clinical-multimodal ultrasound radiomics model constructed with multimodal ultrasound radiomic features and clinical risk factors has favorable potential and high diagnostic value for predicting CLNM in PTC patients.

Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations.

We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide association study (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with the regional DTI-ALPS index. We found 58 genes, including SPPL2C and EFCAB5, which prioritized in the DTI-ALPS index subtypes and associated with neurodegenerative diseases. PheWAS of 241 traits suggested that body mass index and blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted GS function in 44 of 625 predefined disease conditions. Notably, Mendelian randomization and mediation analysis indicated that lower DTI-ALPS index was a risk factor for ischemic stroke (odds ratio = 1.56, P = 0.028) by partly mediating the risk factor of obesity. Results provide insights into the genetic architecture and mechanism for the DIT-ALPS index and highlight its great clinical value, especially in cerebral stroke.

EP72 Assessing the Utility of Abdominal X-Rays in Emergency Settings: Are They Adding Value?

Abstract Background The clinical value of abdominal X-rays (AXRs) in emergency departments (EDs) is debated, particularly with the availability of advanced imaging modalities like ultrasound (US) and computed tomography (CT). Despite the 2016 Royal College of Radiologists (RCR) guidelines limiting AXR use to specific indications, concerns about their overuse persist. Methods A retrospective observational study was conducted from January 1st to March 31st, 2023, in a London district general hospital. We evaluated 473 patients who underwent AXRs, examining compliance with RCR guidelines, clinical indications, AXR findings, follow-up imaging, and referrals to General Surgery. Pearson’s chi-squared test was used for statistical analysis, with significance set at p &amp;lt; 0.05. Results 81.6% of AXRs met RCR guidelines, primarily for suspected bowel obstruction; however, only 11.4% of patients had all three key symptoms (abdominal pain, vomiting, failure to open bowels). Follow-up imaging was performed in 37.6% of cases, mainly CT scans. Abnormal findings were noted in 15% of AXRs, but 63.4% of these required additional imaging. Significant associations were found between abnormal AXRs and General Surgery referrals, as well as between referrals and subsequent CT scans. Conclusions AXRs are frequently overused in the ED, with limited diagnostic value. Even when AXRs identify abnormalities, CT follow-up is often required, suggesting AXRs may not significantly alter management. Reconsidering the role of AXRs in ED practice and promoting advanced imaging modalities could enhance diagnostic efficiency and reduce unnecessary resource use.

A Systematic Review of Micropulse Laser Trabeculoplasty (MLT) in Primary Open-Angle Glaucoma (POAG) Management: Efficacy, Safety, and Future Perspectives

Background/Objectives: Micropulse laser trabeculoplasty (MLT) is gaining attention as a non-invasive treatment option for primary open-angle glaucoma (POAG), offering an alternative to traditional surgeries and medications. This systematic review evaluates the effectiveness, safety, and potential of MLT in glaucoma management. Methods: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, following the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations. Results: We identified 79 articles, and after removing duplicates and screening abstracts, 56 articles were eligible for further review. A detailed full-text analysis was conducted on 26 articles, of which 15 met the predefined inclusion criteria. Conclusions: MLT shows promise as a primary or adjunctive treatment for reducing intraocular pressure (IOP) in glaucoma and ocular hypertension patients. Current evidence supports its efficacy and safety; however, additional long-term studies are needed to confirm its durability and compare its effectiveness with traditional surgical and pharmacological approaches. Standardizing treatment protocols and refining patient selection criteria could enhance MLT’s clinical value and support its broader adoption in glaucoma care.

Activation of the cGAS-sting Pathway Mediated by Nanocomplexes for Tumor Therapy.

cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway is an natural immune response signaling pathway in the human body that is essential for sensing abnormal DNA aggregation in the cell. When the cGAS protein senses abnormal or damaged DNA, it forms a second messenger called cyclic dinucleotide (cGAMP). The cycled dinucleotide will activate the downstream STING protein, thereby inducing the expression of inflammatory cytokines such as type I interferon, which binds to receptors on its own cell membrane and ultimately initiates multiple immune response pathways. This signaling pathway plays an important immune role in antimicrobial and antitumor functions, etc. so the development of drugs targeting this signaling pathway has important clinical application value. In recent years nanocomplexes based cGAS-STING signaling pathway activation and inhibition treatments have been gradually developed. In this review, on the basis of elaborating the main activation mechanism of the cGAS-STING pathway, we further introduced the nanocomplexes that effectively activate the cGAS-STING pathway, focusing on the composition, types and applications of the nanocomplexes. In addition, we discussed the key challenges and future research directions of the way that stimulating the cGAS-STING signaling pathway in the form of nanocomplexes to activate immuno-tumor therapy. Our work aims to provide a better understanding of the progress of nanotherapeutics in the cGAS-STING pathway, providing a promising anti-tumor therapeutic strategy.

Identifying risk factors and constructing a predictive model for heart failure combined with intracardiac thrombus in non-compaction cardiomyopathy patients

This study aims to develop a nomogram prediction model for assessing the cardiogenic composite endpoint, which includes intracardiac thrombosis (ICT) combined with heart failure (HF) in patients with non-compaction cardiomyopathy (NCM) patients. We retrospectively analyzed clinical data from NCM patients (January 2018 to May 2024), who were randomly assigned to training and validation cohorts. Independent predictors were identified using logistic regression, and a nomogram model was developed. The model’s discriminative ability, accuracy, and clinical applicability were subsequently validated. A total of 976 patients were included, of whom 54 had ICT and 191 had HF. Diabetes mellitus (DM), left ventricular end-systolic diameter (LVESD), and ejection fraction (EF) were identified as independent predictors for the composite endpoint. The nomogram demonstrated good performance, with an area under the curve (AUC) of 0.747 (95% CI: 0.707–0.787) in the training group and 0.803 (95% CI: 0.752–0.854) in the validation group. The calibration curve for the training group showed an average absolute error of 0.028, with a Hosmer-Lemeshow test P-value of 0.076. Decision curve analysis and clinical impact curves further indicated that the clinical net benefit was maximized at a threshold probability of 0.05–0.61. This study establishes and validates a nomogram for predicting cardiogenic composite endpoint in NVM patients, demonstrating robust clinical predictive value.

In Silico Evaluation of Algorithm-Based Clinical Decision Support Systems: Protocol for a Scoping Review.

Integrating algorithm-based clinical decision support (CDS) systems poses significant challenges in evaluating their actual clinical value. Such CDS systems are traditionally assessed via controlled but resource-intensive clinical trials. This paper presents a review protocol for preimplementation in silico evaluation methods to enable broadened impact analysis under simulated environments before clinical trials. We propose a scoping review protocol that follows an enhanced Arksey and O'Malley framework and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to investigate the scope and research gaps in the in silico evaluation of algorithm-based CDS models-specifically CDS decision-making end points and objectives, evaluation metrics used, and simulation paradigms used to assess potential impacts. The databases searched are PubMed, Embase, CINAHL, PsycINFO, Cochrane, IEEEXplore, Web of Science, and arXiv. A 2-stage screening process identified pertinent articles. The information extracted from articles was iteratively refined. The review will use thematic, trend, and descriptive analyses to meet scoping aims. We conducted an automated search of the databases above in May 2023, with most title and abstract screenings completed by November 2023 and full-text screening extended from December 2023 to May 2024. Concurrent charting and full-text analysis were carried out, with the final analysis and manuscript preparation set for completion in July 2024. Publication of the review results is targeted from July 2024 to February 2025. As of April 2024, a total of 21 articles have been selected following a 2-stage screening process; these will proceed to data extraction and analysis. We refined our data extraction strategy through a collaborative, multidisciplinary approach, planning to analyze results using thematic analyses to identify approaches to in silico evaluation. Anticipated findings aim to contribute to developing a unified in silico evaluation framework adaptable to various clinical workflows, detailing clinical decision-making characteristics, impact measures, and reusability of methods. The study's findings will be published and presented in forums combining artificial intelligence and machine learning, clinical decision-making, and health technology impact analysis. Ultimately, we aim to bridge the development-deployment gap through in silico evaluation-based potential impact assessments. DERR1-10.2196/63875.

YAP1 induces bladder cancer progression and promotes immune evasion through IL-6/STAT3 pathway and CXCL deregulation.

The Hippo signaling pathway plays a key role in tumorigenesis in different cancer types. We investigated the role of the Hippo effector YAP1 in the tumor immune microenvironment (TIME) of urothelial carcinoma of the bladder (UCB) and evaluated the efficacy of immunotherapy in the context of YAP1 signaling. We performed numerous in vitro and in vivo experiments to determine the role of YAP1 using genetic and pharmacological attenuation of YAP1 activity. Briefly, RNA sequencing was carried out with mouse and human cell lines to identify novel YAP1-regulated downstream targets unbiasedly. We then experimentally confirmed that YAP1 regulates the TIME through the IL-6/STAT3 signaling pathway and varied C-X-C motif chemokine regulation. We analyzed several human sample sets to explore the TIME status in the context of YAP1 expression. Our data indicate that YAP1 attenuation decreases M2 macrophages and myeloid-derived suppressor cells in the TIME compared with YAP1-expressing cells. In summary, this study provides insights into YAP1 signaling as a driver for cancer stemness and an inducer of immunosuppressive TIME. Moreover, the therapeutic efficacy of YAP1 attenuation indicates that combined blockade of YAP1 and immune checkpoints may yield clinical value for treating patients with UCB.

Prognostic value of inflammation and nutritional indicators for sinonasal squamous cell carcinoma: A single-center retrospective study.

Systemic inflammatory and nutritional markers are associated with the prognosis of various cancers. However, their association with sinonasal squamous cell carcinoma (SNSCC) prognosis remains unclear. This study aimed to identify systemic inflammatory and nutritional markers associated with the postoperative prognosis of patients with SNSCC and to clarify the clinical value of these markers. Data from 129 patients with SNSCC were included. The optimal prognostic systemic inflammatory and nutritional markers were identified using the area under the curve. The prognostic value was evaluated using COX regression and subgroup analyses; a nomogram was built based on these data. The advanced lung cancer inflammation index (ALI) and systemic immune-inflammatory index (SII) had higher prognostic values than the other indices; their cut-off values were 27.80 and 791.35, respectively. The nomogram included tumor stage, ALI, and tumor primary site; the calibration and decision curves indicated that the model had good clinical value. The ALI and SII have potential prognostic value for postoperative patients with SNSCC. The nomogram constructed in this study could be used as a tool to assist physicians in making clinical decisions. 4.

Assessing the Value of Further Investment in R&amp;D Using Mixed Methods: A Case Study of Biosensor-Integrated Arteriovenous Grafts

This study illustrates the utility of a mixed-methods approach in assessing the value of an example novel technology—biosensor-integrated self-reporting arteriovenous grafts (smart AVGs). Currently in preclinical development, the device will detect arteriovenous graft stenosis (surveillance-only use case) and treat stenosis (interventional use case). The approach to value assessment adopted in this study was multifaceted, with one stage informing the next and comprised a stakeholder engagement with clinical experts to explore the device’s clinical value, a cost–utility analysis (CUA) from a US Medicare perspective to estimate pricing headroom, and an investment model estimating risk-adjusted net present value analysis (rNPVs) to determine commercial viability. The stakeholder engagement suggested that it would currently be difficult to establish the current value of the surveillance-only use case due to the lack of well-established interventions for preclinical stenosis. Based on this, the CUA focused on the interventional use case and estimated economically justifiable prices at assumed effectiveness levels. Using these prices, rNPVs were estimated over a range of scenarios. This value assessment informs early decision-making on health technology R&amp;D by identifying the conditions (including clinical study success, potential market size and penetration, market access strategies, and assumptions associated with CUA) under which investment may be considered attractive.

The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort

Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear. This study aims to evaluate PRS and define most informative thresholds in relation to conventional clinical and physiological criteria of asthma using a multivariate statistical method. Clinical and genome-wide genotyping data were obtained from the Quebec City Case-Control Asthma Cohort (QCCCAC), which is an independent cohort from previous GWAS. PRS was derived using LDpred2 and integrated with other asthma phenotypes by means of Principal Component Analysis with Optimal Scaling (PCAOS). PRS was considered using ‘ordinal level of scaling’ to account for non-linear information. In two dimensional PCAOS space, the first component delineated individuals with and without asthma, whereas the severity of asthma was discerned on the second component. The positioning of high vs. low PRS in this space matched the presence and absence of airway hyperresponsiveness, showing that PRS delineated cases and controls at the same extent as a positive bronchial challenge test. The top 10% and the bottom 5% of the PRS were the most informative thresholds to define individuals at high and low genetic risk of asthma in this cohort. PRS used in a multivariate method offers a decision-making space similar to hyperresponsiveness in this cohort and highlights the most informative and asymmetrical thresholds to define high and low genetic risk of asthma.

Identification, Clinical Values, and Prospective Pathway Signaling of Lipid Metabolism Genes in Epilepsy and AED Treatment.

The dysregulation of lipid metabolism has been associated with the etiology and progression of the neurological pathology. However, the roles of lipid metabolism and the molecular mechanism in epilepsy and the use of antiepileptic drugs (AEDs) are relatively understudied. Gene expression profiles of GSE143272 from blood samples were included for differential analysis, and the lipid metabolism-related differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks. RT-PCR and western blotting were used to verify the expression levels of lipid metabolism-related DEGs in serum and cerebrospinal fluid (CSF). Eleven lipid metabolism-related DEGs were identified including CXCL8, PTGS2, FOSB, G0S2, HLA-C, CLEC12A, ARG1, ELANE, RSAD2, CTSG, and DEFA1. And among them, five lipid metabolism-related Hub DEGs including CXCL8, PTGS2, ELANE, CTSG, and ARG1 were finally verified in serum samples of epilepsy patients. Moreover, CXCL8 was selected and validated in the epilepsy without AEDs and epilepsy with AEDs. G0S2 was significantly decreased in serum and CSF in epilepsy with AEDs compared to epilepsy without AEDs. Collectively, these findings suggest that lipid metabolism is closely related to epilepsy. This revelation opens up opportunities to further investigate the associated molecular mechanisms and possible therapeutic targets for epilepsy.

Risk factors for plastic bronchitis in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia and establishment of a nomogram model

To investigate the risk factors for plastic bronchitis (PB) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) and to establish a nomogram prediction model. A retrospective analysis was conducted on 178 children with MUMPP who underwent bronchoscopy from January to December 2023. According to the presence or absence of PB, the children were divided into a PB group (49 children) and a non-PB group (129 children). The predictive factors for the development of PB in children with MUMPP were analyzed, and a nomogram prediction model was established. The model was assessed in terms of discriminatory ability, accuracy, and clinical effectiveness. The multivariate logistic regression analysis showed that older age and higher levels of lactate dehydrogenase and fibrinogen were closely associated with the development of PB in children with MUMPP (P<0.05). A nomogram model established based on these factors had an area under the receiver operating characteristic curve of 0.733 (95%CI: 0.651-0.816, P<0.001) and showed a good discriminatory ability. The Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model had a good degree of fit (P>0.05), and the decision curve analysis showed that the model had a good clinical application value. The risk nomogram model established based on age and lactate dehydrogenase and fibrinogen levels has good discriminatory ability, accuracy, and predictive efficacy for predicting the development of PB in children with MUMPP.

Expression of soluble factor-related apoptosis ligand in peripheral blood and microRNA-147b in monocytes in children with sepsis and their association with prognosis

To investigate the expression of soluble factor-related apoptosis ligand (sFasL) in peripheral blood and microRNA-147b (miR-147b) in monocytes in children with sepsis and their value in assessing prognosis. A prospective study was conducted on 124 children with sepsis (sepsis group), 60 children with common infections (infection group), and 60 healthy children undergoing physical examinations (healthy control group). The independent risk factors for poor prognosis in children with sepsis were analyzed, and the value of serum sFasL and monocyte miR-147b in predicting poor prognosis in children with sepsis was assessed. The serum level of sFasL and the relative expression of miR-147b in monocytes were highest in the sepsis group, followed by the infection group and the healthy control group (P<0.05). The multivariate logistic regression analysis showed that the serum level of sFasL and the relative expression of miR-147b in monocytes were closely associated with the poor prognosis of children with sepsis (P<0.05). The receiver operating characteristic curve analysis showed that the combination of serum sFasL level and relative expression of miR-147b in monocytes had a larger area under the curve compared to each indicator alone in predicting the prognosis of children with sepsis (P<0.05). There are significant increases in the level of sFasL in peripheral blood and the relative expression of miR-147b in monocytes in children with sepsis. The combined use of these two indicators has relatively high clinical value in assessing the prognosis of children with sepsis.