Although great progress has been achieved in the techniques and materials of cardiopulmonary bypass (CPB), cardiac surgery under CPB is still one of the surgeries with the highest complication rate. The systemic inflammatory response is an important cause of complications, mainly characterized by activation of innate immune cells and platelets, and up-regulation of inflammatory cytokines. After activation, a variety of molecules on the membrane surface are up-regulated or down-regulated, which can amplify tissue inflammatory damage by releasing cytoplasmic protease and reactive oxygen species, and activate multiple inflammatory signaling pathways in the cell, ultimately leading to organ dysfunction. Therefore, the expression of these cell membrane activation markers is not only a marker of cell activation, but also plays an important role in the process of vital organ injury after surgery. Identification of these specific activation markers is of great significance to elucidate the mechanisms related to organ injury and to find new prevention and treatment methods. This article will review the relationship between these activated biomarkers in the innate immune cells and vital organ injuries under CPB.
ObjectiveTo detect the expression of Ki-67 in papillary thyroid carcinoma (PTC) and investigate its clinical significance. MethodsA retrospective analysis was conducted on PTC patients treated at West China Hospital of Sichuan University from August 2024 to February 2025. The relation between the Ki-67 expression in the postoperative pathological tissues and clinicopathologic features was analyzed. Additionally, the concordance of Ki-67 expression between the preoperative fine-needle aspiration samples and postoperative pathological tissues was evaluated by Bland-Altman analysis. The significance level was set at α=0.05. ResultsA total of 290 PTC patients met the inclusion and exclusion criteria were enrolled. Patients with classical PTC, M1 classification, TNM stage Ⅳ, and those achieving thyroid stimulating hormone (TSH) suppression targets at one month postoperatively had higher Ki-67 expression than those with follicular variant PTC, M0 classification, TNM stages Ⅰ–Ⅲ, or inadequate TSH suppression (all P＜0.05). No significant differences were observed in other subgroups (P>0.05). Furthermore, Bland-Altman analysis of 27 paired samples showed a mean bias of 1.269% between preoperative and postoperative measurements. Elevated variability occurred in high Ki-67 cases, with 11.1% (3/27) exceeding ±6% limits of agreement. ConclusionsThe study demonstrates that Ki-67 expression correlates with malignant attributes including tumor aggression and advanced disease. It may serve as a prognostic biomarker for assessing malignant potential in PTC.
ObjectiveTo summarize the new biomarkers of deep venous thrombosis (DVT) and their research progress, so as to provide new ideas for the prevention, diagnosis and treatment of DVT. MethodThe literature about biomarkers of DVT in recent 5 years was reviewed and summarized. ResultsAccording to the results of literature review, a variety of common DVT biomarkers such as serum microrna, fibrin monomer, neutrophil capture net, and E-selectin were sorted out, but most of them had not been used in clinical DVT management. At present, the clinical diagnosis of DVT required the combination of positive D-dimer test and positive imaging examination, and there was no single biomarker for the diagnosis of DVT. ConclusionsBiomarkers are valuable in the diagnosis and treatment of DVT, but their sensitivity and specificity need to be optimized. Therefore, finding biomarkers with more diagnostic value is one of the future directions. At the same time, we also can consider fully combined with a variety of existing biomarkers, to improve the efficiency to the diagnosis of DVT.
Objective To explore the role of cyclin B1 (CCNB1), cyclin B2 (CCNB2) and cyclin dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) using bioinformatic data. Methods First, RNA expression data were downloaded from two datasets in Gene Expression Omnibus (GEO), and DESeq2 software was used to identify deferentially expressed genes (DEGs). Subsequent analyses were conducted based on the results of these DEGs: protein-protein interaction (PPI) network was constructed with STRING database; the modules in PPI network were analyzed by Molecular Complex Detection software, and the most significant modules were selected, the genes included in these modules were the hub genes; high-throughput RNA sequencing data from other databases were used to verify the expression of these hub genes to confirm whether they were DEGs; survival curve analyses of the confirmed DEGs were conducted to select genes that had significant influence on the survival of LUAD; the expression of these hub genes in different stages of LUAD were also analyzed. Then, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for these selected hub genes using KOBAS database. MuTarget tool was used to analyze the correlations between the expression of these selected hub genes and gene mutation status in LUAD. The potential value of these hub genes in the treatment of LUAD was explored based on the drug information in GDSC database. Finally, immunohistochemical data from Human Protein Atlas (HPA) database were used to verify the expression of these hub genes in LUAD again. Results According to the expression data in GEO, 594 up-regulated genes and 651 down-regulated genes were identified (P<0.05), among which 30 hub genes were selected for subsequent analyses. The RNA high-throughput sequencing data of other databases verified that 18 genes were DEGs, among which 8 hub genes had significant impact on disease-free survival in LUAD (P<0.05). Moreover, the 8 genes were differentially expressed in different stages of LUAD, which were higher in the middle and late stage of LUAD. Among the 8 genes. CCNB1, CCNB2 and CDK1 were significantly enriched in the cell cycle pathway. The expression of CCNB1, CCNB2 and CDK1 in LUAD was closely related to the TP53 mutation status. In addition, CDK1 was associated with four drugs, revealing the potential value of CDK1 in the treatment of LUAD. Finally, immunohistochemical data from HPA database verified that CCNB1, CCNB2 and CDK1 were highly expressed in LUAD in the protein level. Conclusion Overexpression of CCNB1, CCNB2 and CDK1 are associated with poor prognosis of LUAD, indicating that the three genes may be prognostic biomarkers of LUAD and CDK1 is a potential therapeutic target for LUAD.
ObjectiveTo explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). MethodsA systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). ResultsA total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. ConclusionThe exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.
Objective The management of pulmonary nodules is a common clinical problem, and this study constructed a nomogram model based on FUT7 methylation combined with CT imaging features to predict the risk of adenocarcinoma in patients with pulmonary nodules. Methods The clinical data of 219 patients with pulmonary nodules diagnosed by histopathology at the First Affiliated Hospital of Zhengzhou University from 2021 to 2022 were retrospectively analyzed. The FUT7 methylation level in peripheral blood were detected, and the patients were randomly divided into training set (n=154) and validation set (n=65) according to proportion of 7:3. They were divided into a lung adenocarcinoma group and a benign nodule group according to pathological results. Single-factor analysis and multi-factor logistic regression analysis were used to construct a prediction model in the training set and verified in the validation set. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the model, the calibration curve was used to evaluate the consistency of the model, and the clinical decision curve analysis (DCA) was used to evaluate the clinical application value of the model. The applicability of the model was further evaluated in the subgroup of high-risk CT signs (located in the upper lobe, vascular sign, and pleural sign). Results Multivariate logistic regression analysis showed that female, age, FUT7_CpG_4, FUT7_CpG_6, sub-solid nodules, lobular sign and burr sign were independent risk factors for lung adenocarcinoma (P<0.05). A column-line graph prediction model was constructed based on the results of the multifactorial analysis, and the area under the ROC curve was 0.925 (95%CI 0.877 - 0.972 ), and the maximum approximate entry index corresponded to a critical value of 0.562, at which time the sensitivity was 89.25%, the specificity was 86.89%, the positive predictive value was 91.21%, and the negative predictive value was 84.13%. The calibration plot predicted the risk of adenocarcinoma of pulmonary nodules was highly consistent with the risk of actual occurrence. The DCA curve showed a good clinical net benefit value when the threshold probability of the model was 0.02 - 0.80, which showed a good clinical net benefit value. In the upper lobe, vascular sign and pleural sign groups, the area under the ROC curve was 0.903 (95%CI 0.847 - 0.959), 0.897 (95%CI 0.848 - 0.945), and 0.894 (95%CI 0.831 - 0.956). Conclusions This study developed a nomogram model to predict the risk of lung adenocarcinoma in patients with pulmonary nodules. The nomogram has high predictive performance and clinical application value, and can provide a theoretical basis for the diagnosis and subsequent clinical management of pulmonary nodules.
ObjectiveTo explore the predictive value of N-terminal-pro-brain natriuretic peptide (NT-ProBNP) for postoperative early outcomes in infants with aortic coarctation (CoA).MethodsA retrospective study was conducted in 344 children with CoA admitted to our hospital from September 2014 to October 2017, including 206 males (59.9%) and 138 females (40.1%), with an average age of 0.2-60.0 (7.1±10.6) months. The levels of NT-proBNP, clinical characteristics, imaging data and early follow-up results were collected and analyzed.ResultsCompared with the normal NT-proBNP group, there were statistical differences in age, the proportion of RACHS-1≥3, the proportion of preoperative pneumonia and dysplastic aortic arch, preoperative cardiac function, left ventricular wall thickness, left ventricular dilatation, hospital stay, ICU duration, ventilator duration, duration of vasoactive drugs use, delayed chest closure, nasal continuous positive airway pressure (nCPAP), postoperative cardiac insufficiency in the abnormal NT-proBNP group (P<0.05). According to multivariate logistic regression analysis, NT-proBNP level (>3 000 pg/mL) was an independent risk factor for prolonged ICU duration [OR=3.17, 95%CI (1.61, 6.23)], prolonged ventilator duration [OR=5.84, 95%CI (2.86, 11.95)], prolonged use of vasoactive drugs [OR=2.22, 95%CI (1.22, 4.02)], postoperative cardiac insufficiency [OR=3.10, 95%CI (1.64, 5.85)]; NT-proBNP level (> 5 000 pg/mL) was an independent risk factor for delayed chest closure [OR=3.55, 95%CI (1.48, 8.50)].ConclusionNT-proBNP level in children with CoA can be affected by many factors, including age, complexity of congenital heart disease, preoperative cardiac insufficiency, et al. The level of NT-proBNP has predictive value for postoperative early outcomes.
Fibroblast growth factor 21 (FGF21) is a multi-effect endocrine factor, mainly secreted in liver and adipose tissue, with the properties of lipid-lowering, anti-inflammatory, anti-oxidant and anti-atherosclerosis. Recent studies found that FGF21 can induce protective effect in cardiovascular disease, and plasma FGF21 levels in patients with disease cardiovascular are elevated. These studies have suggested the use of FGF21 as a biomarker for subclinical atherosclerosis and its potential role in the treatment of established atherosclerotic cardiovascular disease. This article will review the recent advances in the anti-atherosclerosis effect of FGF21.
Metaiodobenzylguanidine (MIBG) is an analog of norepinephrine that accumulates in sympathetic nerve endings soon after intravenous administration. The degree of accumulation reflects the uptake, storage and release of transmitters by noradrenergic neurons. Myocardial imaging with 123I labeled MIBG (123I-MIBG) can be used to estimate the extent of local myocardial sympathetic nerve damage, which has been widely used in the diagnosis and treatment of various heart diseases. In recent years, numerous studies have been carried out on the application of 123I-MIBG in the diagnosis of degenerative diseases of the nervous system (such as Parkinson's disease and dementia of Lewy body), and have made some achievements. The purpose of this review is to summarize the current clinical application of 123I-MIBG myocardial imaging in the diagnosis of dementia with Lewy bodies, the problems in imaging technology and the possible research directions in the future, so as to provide valuable reference information for clinicians to reasonably and accurately apply this technology in the early diagnosis and discrimination of dementia.
Objective To investigate activated toll-like receptor-4 (TLR4) signaling pathway involved in pathophysiological mechanisms of type A aortic dissection (TAAD). Methods Specimens of full-thickness ascending aorta wall from the TAAD patients (n=12) and the controlled donors (n=12) were collected. Western blotting was used to examine the associated proteins' expression of TLR4 signaling pathway. Blood samples from TAAD (n=43) and controlled patients (n=50) were examined by enzyme-linked immunosorbent assay (ELISA) to detect the circulating plasma cytokines levels of interleukin-1β (L-1β). Results In the aortic wall of TAAD, expression levels of TLR4 and protein expression of major molecule significantly elevated, and activated macrophages increased. Furthermore, elevated IL-1β levels were observed in the TAAD patients’ plasma compared with the control plasma. Multiple logistic regression analysis and receiver operating characteristic (ROC) curve showed that elevated IL-1β could be a novel and promising biomarker with important diagnostic and predictive value in the identification of TAAD. Conclusion Activated TLR4/NF-κB signaling pathway regulates inflammatory response to involve in pathophysiological mechanisms of type A aortic dissection and its regulated inflammatory products have important predictive value for patients with TAAD.