Annals of medicine最新文献

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the axial joints. Immune cells play a key role in the pathogenesis of AS. This study integrated bioinformatics methods with experimental validation to explore the role of natural killer (NK) cells in AS.

Methods: Two microarray datasets, GSE25101 and GSE73754, were selected, and the scRNA-seq data were obtained from GSE194315 and Liu's research. Differentially expressed genes (DEGs) and functional enrichment analysis were performed respectively. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules of co-expressed genes and genes involved in NK cell function. The diagnostic value of the identified key genes was evaluated using ROC curves, logistic regression analysis, and a nomogram. Real-time PCR (RT-PCR) was used to quantified the expression of genes. Statistical analysis was conducted using the R software package, and a p-value of less than 0.05 was considered statistically significant.

Results: Pathways enrichment analysis revealed the involvement of NK cell-mediated immune pathways and regulation of the innate immune response, indicating the crucial role of innate immunity, especially NK cells, in AS pathogenesis. The construction of a co-expression network revealed that the MElightyellow module was most relevant to the NK cell-mediated immune pathway. IL2RB, CD247, PLEKHF1, EOMES, S1PR5, FGFBP2 from the MElightyellow module were identified as key genes involved in NK cell-mediated immune response and served as potential diagnostic biomarkers for AS, with moderate to high diagnostic values based on AUC values. Further analysis using scRNA-seq profiling revealed the higher expression level of IL2RB, CD247, PLEKHF1, S1PR5, FGFBP2 in NK cells compared to that in other cell types. CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 were reduced expressed in AS patients as compare to control group verified by scRNA-seq data, CD247, EOMES, FGFBP2, IL2RB and S1PR5 were reduced expressed verified by RT-PCR, and PLEKHF1, S1PR5, and FGFBP2 was upregulated after TNF-α blocker therapy.

Conclusion: The study revealed the potential role of NK cells and identified IL2RB, CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 as key genes associated with NK cells in the pathogenesis of AS.

Background: Although existing studies have identified some genetic loci associated with chronic obstructive pulmonary disease (COPD) susceptibility, many variants remain to be discovered. The aim of this study was to further explore the potential relationship between IL18R1 single nucleotide polymorphisms (SNPs) and COPD risk.

Methods: Nine hundred and ninety-six subjects were recruited (498 COPD cases and 498 healthy controls). Five candidate SNPs of IL18R1 were selected and genotyped using MassARRAY iPLEX platform. Logistic regression analysis was performed to assess the association of these SNPs with COPD risk. Multifactor dimensionality reduction (MDR) software was applied to calculate the interaction of SNP-SNP on COPD risk.

Results: IL18R1 rs9807989 (OR = 0.42, p < .001), rs3771166 (OR = 0.40, p < .001) and rs6543124 (OR = 0.44, p < .001) were associated with the reduced COPD risk, while rs2287037 (OR = 2.71, p < .001) and rs2058622 (OR = 2.06, p < .001) might be the risk-increasing factor for COPD occurrence in both the overall analysis and subgroup analysis (age, gender, drinking, and smoking). The best multi-locus model was the combination of rs2058622 and rs3771166.

Conclusion: Our study provided a reference and basis for investigating the association of IL18R1 polymorphisms with COPD risk.

Objective: We aimed at identifying acute phase biomarkers in Severe Fever with Thrombocytopenia Syndrome (SFTS), and to establish a model to predict mortality outcomes.

Methods: A retrospective analysis was conducted on multicenter clinical data. Group-based trajectory modeling (GBTM) was utilized to demonstrate the overall trend of laboratory indicators and their correlation with mortality. Six different machine learning algorithms were employed to develop prognostic models based on the clinical features during the acute phase, which were reduced using Lasso regression.

Results: Seven indicators (ALT, AST, BUN, LDH, a-HBDH, DD, and PLT) at 7-10 days post-onset and their change slopes were found to be crucial during disease progression. These, along with other clinical features, were reduced to 8 variables using Lasso regression for model construction. The random forest model demonstrated the best performance in both internal validation (AUC: 0.961) and external validation (AUC: 0.948). Decision Curve Analysis indicated a good balance between model benefits and risks.

Conclusions: a-HBDH and its change slope along with central nervous symptom manifestations within 7-10 days after onset accurately predicted mortality in SFTS. Various algorithms provided a comprehensive overview of disease progression and constructed more stable and efficient models.

Introduction: Esketamine has unique advantages in combination with dexmedetomidine for sedation in young children, owing to its sympathetic activity and mild respiratory depression. However, the optimal dose is yet to be determined. In this study, we compared the different doses of intranasal esketamine combined with dexmedetomidine for sedation during transthoracic echocardiography in toddlers.

Patients and methods: A total of 121 eligible children aged 13 years, who were scheduled for transthoracic echocardiography were randomized into three groups. They were treated with intranasal dexmedetomidine 1 mcg.kg^-1 + esketamine 0.5 mg.kg^-1 (group S1), dexmedetomidine 1 mcg.kg^-1 + esketamine 1 mg.kg^-1 (group S2), or dexmedetomidine 1 mcg.kg^-1 + esketamine 1.5 mg.kg^-1 (group S3). The primary outcome was the success rate of sedation, other outcomes included HR, SpO₂, onset time, wake-up time, and adverse effects.

Results: The success rate of sedation was significantly higher in groups S2 (85.4%) and S3 (87.5%) than ingroup S1 (60%) (p = 0.004). The baseline HR and SpO₂ did not differ between the groups at the corresponding time points following drug administration. The onset time and duration of sedation in group S1 were significantly longer than those in groups S2 and S3 (p = 0.000). However, there were no differences in the wake-up time or adverse effects among the three groups.

Conclusions: Intranasal administration of 1 mg.kg^-1 esketamine combined with 1 mcg.kg^-1 dexmedetomidine provided satisfactory sedation in young children undergoing transthoracic echocardiography. This sedative approach offers a rapid onset of awakening with few side effects.

Clinical trial registration number: ChiCTR2200060976, 2022/06/14 (trail from August 2022 to January 2023).

Background: Much remains to be learned about patients with heart failure with improved ejection fraction (HFimpEF).

Objective: This study sheds light on the characteristics and clinical outcomes of HFimpEF patients, including the consequences of halting guideline-directed medical therapy (GDMT).

Methods: This retrospective study was conducted on patients diagnosed with heart failure with reduced ejection fraction (HFrEF) who underwent a second echocardiogram at least 6 months apart between January 2009 and February 2023. The primary outcomes were major adverse cardiovascular events (MACEs), including all-cause mortality and heart failure hospitalization. The second outcome was recurrent HFrEF.

Results: Of 4,560 HFrEF patients were included, 3,289 (72.1%) achieved HFimpEF within a median follow-up period of 3.4 years (IQR: 1.8 - 5.9 years). Among these HFimpEF patients, recurrent HFrEF was observed in 941 (28.6%) patients during a median follow-up period of 2.3 years (IQR: 0.8-4.6 years). The proportion of patients who halted GDMT was 70.4%, 53.2%, 59.8% and 63.8% for MRA, beta-blockers, ACEI/ARB/ARNI and SGLT-2 inhibitors. Multivariable Cox analysis revealed ischemic heart disease, chronic kidney disease, coronary heart disease, lower left ventricular ejection fraction, larger left ventricular diastolic dimension and non-use GDMT are associated with recurrent HFrEF. Individuals without GDMT use exhibited lower chances of persistently recovering ejection fraction and high risks of MACEs compared to those who continue use.

Conclusions: HFimpEF is a common condition across all clinical follow-ups. Prevalent discontinuation of GDMT medications may contribute significantly to recurrent HFrEF, placing patients at a higher risk for poor prognosis.

Background: Programmed death ligand-1 (PD-1), as an immunotherapy target, has been increasingly used in tumour therapies. But as reactions and outcomes to PD-1 inhibitors combined with chemotherapy vary individually, it is primarily important to identify an ideal indicator for predicting the therapeutic effectiveness in individual patients. Oesophageal cancer (EC) patients often have difficulty eating due to tumour blockage of the oesophagus, leading to malnutrition and muscle loss. Sarcopenia is one of the influencing factors for poor prognosis in tumour patients, but its role in PD-1 inhibitors combined with chemotherapy of EC patients is not fully clarified. In this study, we aimed to explore the prognostic significance of Sarcopenia measured by CT in EC patients treated with PD-1 antibody combined with chemotherapy.

Methods: The third lumbar skeletal muscle mass index (L3-SMI) was obtained from 83 EC patients before and 3 months after administration of PD-1 inhibitors combined with chemotherapy using conventional CT scans.

Results: Baseline L3-SMI and 3-month L3-SMI values were found not suitable for predicting the overall survival (OS) of EC patients (p = 0.32 & p = 0.055). Longitudinal change in L3-SMI (ΔL3-SMI) during PD-1 inhibitors combined with chemotherapy was identified as a relevant marker of OS in univariable analysis (HR: 0.98, 95% CI: 0.96-1.00, p = 0.042) and multivariable analysis (HR: 0.96, 95% CI: 0.93-0.99, p = 0.02). L3-SMI-positive patients generally had better OS (p = 0.041).

Conclusion: Excessive muscle loss rather than muscle loss before and after administration of PD-1 inhibitors combined with chemotherapy is an important prognostic factor for therapeutic outcomes and OS in EC patients.

Objectives: Intervertebral disc degeneration (IVDD) is a prevalent degenerative condition associated with a high incidence rate of low back pain and disability. This study aimed to identify potential biomarkers and signaling pathways associated with IVDD.

Methods: Biomarkers were discerned through bulk-RNA and single-cell RNA sequencing (scRNA-Seq) investigations of IVDD cases from the Gene Expression Omnibus (GEO) database. Following this, two central genes were identified. Furthermore, gene set enrichment analysis (GSEA) and receiver operating characteristic (ROC) curve analysis were conducted. The transcriptional factor (TF) derived from nucleus pulposus (NP) cells was examined through the DoRothEA R package. RT-qPCR and IHC techniques were employed to confirm the expression of the two hub genes and their associated genes in tissue samples.

Results: The proteins Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) and collagen VI-α2 (COL6A2) were frequently analyzed using a combination of DEGs from datasets GSE70362, GSE124272, and scRNA-seq. Examination of gene expression across multiple datasets indicated significant differences in TNFAIP6 and COL6A2 levels in IVDD compared to control or normal groups (p < 0.05). These two central genes demonstrated strong diagnostic utility in the training cohort and reliable predictive value in the validation datasets. Our study verified the potential role of ZEB2 as a TF in regulating two key genes associated with IVDD. Furthermore, qPCR and IHC confirmed elevated expression levels of the hub genes and transcription factor.

Conclusion: We identified biomarkers, specifically TNFAIP6 and COL6A2, that have the potential to predict disease activity and aid in the diagnosis of IVDD.

Purpose: This study quantified the impact of clinical clerkships on medical students' disciplinary knowledge using the Comprehensive Clinical Science Examination (CCSE) as a formative assessment tool.

Methods: This study involved 155 third-year medical students in the College of Human Medicine at Michigan State University who matriculated in 2016. Disciplinary scores on their individual Comprehensive Clinical Science Examination reports were extracted by digitizing the bar charts using image processing techniques. Segmented regression analysis was used to quantify the differences in disciplinary knowledge before, during, and after clerkships in five disciplines: surgery, internal medicine, psychiatry, pediatrics, and obstetrics and gynecology (ob/gyn).

Results: A comparison of the regression intercepts before and during their clerkships revealed that, on average, the participants improved the most in ob/gyn ($\beta =$11.193, p$<$.0001), followed by psychiatry ($\beta =$10.005, p$<$.001), pediatrics ($\beta =$6.238, p$<$.0001), internal medicine ($\beta =$1.638, p$=$.30), and improved the least in surgery ($\beta =$-2.332, p$=$.10). The regression intercepts of knowledge during their clerkships and after them, on the other hand, suggested that students' average scores improved the most in psychiatry ($\beta =$7.649, p$=$.008), followed by ob/gyn ($\beta =$4.175, p$=$.06), surgery ($\beta =$4.106, p$=$.007), and pediatrics ($\beta =$1.732, p$=$.32).

Conclusions: These findings highlight how clerkships influence the acquisition of disciplinary knowledge, offering valuable insights for curriculum design and assessment. This approach can be adapted to evaluate the effectiveness of other curricular activities, such as tutoring or intersessions. The results have significant implications for educators revising clerkship content and for students preparing for the United States Medical Licensing Examination Step 2.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that severely impairs patients' respiratory function and quality of life. RARB is involved in COPD progression by affecting inflammatory reactions, cell proliferation, and apoptosis. The impact of single nucleotide polymorphisms (SNPs) within RARB on COPD susceptibility remains unclear. Here, we aimed to evaluate the association between RARB SNPs and COPD risk.

Methods: A total of 270 COPD patients and 271 healthy controls were enrolled. The MassARRAY iPLEX platform tested the genotype of the SNPs. The association was analyzed using logistic regression analysis. The false-positive report probability (FPRP) analysis was performed to validate the significant findings. The relationship between SNPs and RARB expression was evaluated using the GTEx database.

Results: Our study found a significant association between rs6799734 and COPD susceptibility (OR 1.88, p = 0.008, p (FDR) = 0.047). The stratified analysis revealed that this association was particularly pronounced among individuals aged ≤ 71 years (OR 2.34, p = 0.011, p (FDR) = 0.045), males (OR 2.60, p = 0.002, p (FDR) = 0.013), those with a BMI ≥ 24 (OR 3.95, p = 0.018, p (FDR) = 0.108), and smokers (OR 2.48, p = 0.020, p (FDR) = 0.120). Additionally, rs1286641 and rs1881706 showed significant associations with COPD risk in females and smokers. These associations were further validated by FPRP analysis. Preliminary mechanism studies indicated that rs1286641 and rs1881706 were related to RARB expression.

Conclusion: Our findings suggest a potential role of RARB SNPs in influencing COPD risk.

Objectives: Platelet transfusion refractoriness (PTR) is a frustrating clinical problem, and primary and persistent (P/P) PTR who experienced persistent PTR since the first transfusion was failed to be well recognized. This study aims to investigate the incidence and risk factors for P/P PTR.

Methods: Patients with hematologic disorders who underwent HLA high-resolution genotyping and donor-specific HLA antibody or panel reactive antibody (PRA) testing between January 2019 and March 2023 were reviewed. Clinical data including infection history, splenomegaly, frequency and quantity of blood transfusions, and transfusions response were delineated and subsequently analyzed.

Results: 114 patients were included retrospectively, and 1071 transfusions were recorded. The overall incidence of PTR was 28.95% (33/114), with 63.63% (21/33) being P/P PTR. Anti class I HLA (anti-HLA-I) antibody was identified as an independent risk factor for ineffective platelet transfusion through multivariate logistic regression analysis (p = .034). Interestingly, anti-HLA-C autoantibodies were first found in six patients, and both anti-HLA-A and C autoantibodies were detected in one case, comprising a total of 10.71% (6/56) of HLA-I antibody-positive patients. Further analysis revealed that anti-HLA-C autoantibody was identified as an independent risk factor for P/P PTR (p = .039). Among patients with positive anti-HLA-C antibodies, significant differences in the effectiveness of ABO, D-matched and cross-matching transfusions were observed between patients with or without anti-HLA-C autoantibodies (p < .001 and p = .017). Notably, platelet transfusions independence was achieved by two of the four patients who received rituximab.

Conclusions: This work emphasized the significance of anti-HLA-C autoantibody for P/P PTR in hematological patients, and rituximab may therapeutic.