ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
Objective To investigate the association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke. Methods We screened patients with acute ischemic stroke admitted to the Department of Neurology, West China Hospital of Sichuan University between January and December 2022. The case group consisted of patients who developed malignant brain edema within 7 days of admission, while the control group consisted of patients who did not develop malignant brain edema within 7 days of admission. Multivariate logistic regression analysis was used to explore the association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke. Results Finally, 428 patients were included, aged 70.00 (58.00, 82.00) years, with females accounting for 40.9% (n=175). The time from onset to admission was 10.00 (4.00, 24.00) hours. Forty-three patients (10.0%) developed malignant brain edema and were classified as the case group, and their onset time of malignant brain edema was 34.00 (22.50, 56.50) hours after the onset of the disease. Multivariate logistic regression analysis showed that the increase in the score of the baseline National Institutes of Health Stroke Scale scores [odds ratio (OR)=1.167], the combination of diabetes (OR=5.525), the treatment of thrombectomy (OR=23.875), and the neutrophil percentage-to-albumin ratio higher than the median (OR=3.806) were associated with the increased risk of malignant brain edema (P<0.05), and the successful reperfusion after thrombectomy (OR=0.120) was associated with the reduced risk of malignant brain edema (P<0.05). Conclusion A higher percentage of serum neutrophil percentage-to-albumin ratio within 24 hours of onset in patients with acute ischemic stroke is associated with an increased risk of malignant brain edema within 7 days of admission.
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.
The nucleic acid adapters of tumor serum markers are oligonucleotide molecules with high specificity and high affinity with tumor serum markers obtained by in vitro screening with systematic evolution of ligands by exponential enrichment (SELEX). Researchers take the advantage of the nucleic acid adapter to explore new tumor serum markers that have more diagnostic value for tumor diagnosis. Recently, some achievements have been achieved in the research of liver cancer and stomach cancer. This paper has reviewed nucleic acid adapter and its research in the serum tumor marker screening, and discussed the value of the nucleic acid adapter of serum tumor markers in the diagnosis, as well as current problems existing in the research. This paper is very useful to help people better understand the screening of nucleic acid adapters of tumor serum markers, and to provide help in discovering new tumor serum markers.
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 summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
Circular RNA (circRNA) is a non-coding RNA which exists widely in eukaryotic cells with a structure of covalently closed continuous loop. Its generation, characteristics and functions have received extensive attention, making it one of the hot spots in the field of non-coding RNA research. Many studies have found that circRNA plays an important role in the development of various diseases including cardiovascular disease, nervous system disease and cancer. Cardiovascular disease is a worldwide common disease with high incidence and poor prognosis. Its exact pathogenesis has not been found, which blocks the development of cardiovascular disease treatment. In this review, we summarize the loop-forming mechanisms, the functions and the progress of current researches of circRNA in cardiovascular diseases.
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 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.
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.