Ischemic heart disease (IHD) refers to a condition with myocardial ischemia, hypoxia, and even cardiomyocyte death due to coronary artery stenosis or occlusion. Energy metabolism gets disturbed by imbalanced ATP synthesis and degradation, while conversion of hypoxanthine to xanthine degraded from ATP synchronously provokes excessive reactive oxygen species (ROS). Metabolic disturbance and oxidative stress are pivotal features of IHD, both of which are associated with increased purine catabolizing enzyme activity of xanthine oxidoreductase (XOR). Here, we construct mushroom-like asymmetric nanozyme (CeAu MAN) through symmetry-breaking synthesis of ceria and gold nanoparticles, which function with XOR-inhibitory effects in cardiac purine metabolism. Mechanistically, superior superoxide dismutase (SOD)-like and catalase (CAT)-like activities of CeAu MAN reduce intracellular ROS levels and diminish oxidative stress-induced cardiomyocyte apoptosis. As revealed by metabolomics in conjunction with purine-related metabolites, CeAu MANs constrain purine degradation pathways by inhibiting metabolic conversion of xanthine into uric acid in the injured myocardium through a heterointerface-mediated affinity to XOR. We also demonstrated therapeutic efficacy of CeAu MANs in MI/RI mice including improved heart function, attenuated maladaptive remodeling, and reliable biocompatibility in three weeks. Symmetry-breaking mushroom-like CeAu MANs improve cardiac purine catabolism and spark an innovative paradigm in metabolic therapy of IHD.

This study is aimed at systematically identifying key genes associated with EGFR mutations and developing a molecular classification model in lung adenocarcinoma (LUAD) using integrative bioinformatics approaches. Multi-omics datasets derived from cBioPortal and The Cancer Genome Atlas (TCGA) LUAD cohort were interrogated to identify genes correlated with EGFR mutational status. A core set of 18 genes exhibiting significant associations with both EGFR mutation frequency and patient prognosis was identified. Based on this gene signature, a two-cluster molecular subtype stratification was established. These subtypes demonstrated statistically significant divergence in overall survival, immune cell infiltration profiles, and predicted responsiveness to immunotherapeutic intervention. Further analyses, including machine learning algorithms, multivariate Cox regression, and molecular docking, identified TRAF2 as a key prognostic gene closely associated with EGFR. In vitro experiments demonstrated that TRAF2 promotes proliferation, migration, and invasion of LUAD cells. Additional analyses suggested that TRAF2 may contribute to tumor progression through epigenetic regulation and associated signaling pathways. Collectively, these findings provide novel insights into the molecular heterogeneity of EGFR-mutant LUAD and offer potential targets for precision prognostic assessment and combination therapeutic strategies.

Research objectivesFull-thickness skin defects present substantial challenges to the healing process, arising from the loss of the dermal layer, inadequate vascular supply, and insufficient growth factor availability. Although previous studies have established that growth factors and platelet-rich plasma (PRP) individually promote tissue repair, the synergistic benefits of their combined application for achieving superior therapeutic outcomes remain unclear. Here, we introduce a novel composite biomaterial: a hydrogel integrating nanoparticles loaded with basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) genes (bFGF/VEGFA NPs) with PRP (termed bFGF/VEGFA@PRP hydrogel), engineered to enable the synergistic delivery of growth factors and bioactive components.MethodsIn this study, we hypothesized that the bFGF/VEGFA@PRP hydrogel can promote wound healing. This hypothesis was tested through various experimental perspectives and methods including material characterization, wound healing rate, wound blood flow signal intensity, skin attachment, cell proliferation, apoptosis, collagen deposition, and growth factor levels.ResultsIn a rat cutaneous wound model, this hydrogel accelerated wound closure, enhanced local blood perfusion, and increased the density of skin appendages and collagen fibers. Mechanistic investigations revealed upregulated expression of angiogenic factors bFGF, VEGFA, and platelet and endothelial cell adhesion molecule 1 (CD31), the anti-apoptotic protein BCL2, the cell proliferation marker Ki67, and type III collagen (COL III) in the treated group.ConclusionsCollectively, these results demonstrate that the bFGF/VEGFA@PRP hydrogel promotes wound healing through the synergistic enhancement of growth factor expression, angiogenesis, and COL III deposition. The combination of gene therapy with PRP treatment was found to be more effective than either modality alone. This study establishes a promising therapeutic strategy for managing complex full-thickness skin injuries.

Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Adrenergic signal has always been considered as an important link with the occurrence and development of cancer. Considerable evidence suggests that β-2 adrenergic receptor (ADRB2) shows an important role in regulating many types of human cancer. But the role of ADRB2 in LUAD is still uncovered. To elucidate the expression of ADRB2 in LUAD, a comprehensive analysis was conducted utilizing the GEO database, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry on human LUAD tissue samples. Subsequent to the modulation of ADRB2 expression in various LUAD cell lines, assessments of cell viability, invasion, and migratory capacity were performed using the Cell Counting Kit-8 (CCK8) assay and transwell chamber assays, respectively. Furthermore, Gene Set Enrichment Analysis (GSEA) was employed to identify relevant pathways, which were subsequently validated through western blot analysis. Furthermore, the STRING database was utilized to predict that TRIM22 is the most significant interacting protein of ADRB2, a finding subsequently validated through immunoprecipitation assays. The cell cycle was analyzed using flow cytometry. The upregulated expression of ADRB2 observed in datasets GSE11969 and GSE68465 was corroborated by analyses of human LUAD tissues and was found to be associated with advanced disease stages. Overexpression of ADRB2 in A549 cells led to increased cell proliferation, migration, and invasion, which were associated with the activation of the JAK2/STAT3 signaling pathway. However, suppressing ADRB2 expression in H1299 cells resulted in reduced cell proliferation, migration, and invasion. Mechanistically, TRIM22 was found to interact with ADRB2, and negatively regulated ADRB2 expression and JAK2/STAT3 signaling pathway. Moreover, inhibition of the JAK2/STAT3 signaling pathway significantly affected cell cycle and suppressed cell proliferation in LUAD cells. Our findings suggest that weakened TRIM22 increased ADRB2 that activated the JAK2/STAT3 signaling pathway, thereby promoting LUAD development.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Chemotherapy, including cisplatin, plays a pivotal role in its treatment; however, the development of cisplatin resistance presents a major clinical challenge. The PSENEN gene, which encodes a regulatory protein, is overexpressed in numerous malignancies. This study explores the role of PSENEN in mediating cisplatin resistance in non-small cell lung cancer (NSCLC). RNA sequencing revealed significant upregulation of PSENEN in cisplatin-resistant A549/DDP cells. Functionally, PSENEN inhibition reversed cisplatin resistance, inhibited cell proliferation and metastasis, and enhanced programmed cell death in A549/DDP cells. Single-cell RNA sequencing indicated that PSENEN was expressed in both cancer and stromal cells. Further functional studies suggested that PSENEN regulates chemoresistance through interactions within the stromal microenvironment. Differentially expressed protein analysis (DIA) of stromal cell supernatants, coupled with functional assays, identified PPIB as a key mediator of PSENEN's effect on lung cancer cell drug resistance via stromal signaling. In vivo, pharmacological inhibition of PSENEN significantly suppressed subcutaneous tumor growth. Additionally, analysis of the immune microenvironment revealed a strong correlation between PSENEN expression and the infiltration of multiple immune cell types. Multiple immunofluorescence and immunohistochemistry validation confirmed that PSENEN is positively correlated with CD56 and PD-1, suggesting its potential application value in immunotherapy.

To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.

Background and Objective:Lung cancer continues to be the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Although targeted therapies and immune checkpoint inhibitors have improved clinical outcomes for NSCLC patients, primary and acquired resistance remain significant obstacles to effective treatment. This review aims to elucidate the molecular mechanisms of NSCLC resistance and explore the potential of nanotechnology-based drug delivery systems in overcoming these resistance barriers. Methods:The research team conducted a comprehensive literature search in PubMed, Cochrane Library, Google Scholar, Embase, Web of Science, China National Knowledge Internet (CNKI), and Wanfang Database, covering the period from January 1st, 2007 to January 1st, 2024. Key Content and Findings:This review summarizes the molecular mechanisms of NSCLC resistance, including target alterations, bypass signaling pathways, phenotypic transformations, and immunosuppressive mechanisms. It discusses the use of nanotechnology-based drug delivery systems (such as polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles) to overcome various resistance barriers. Additionally, it highlights the role of nanotechnology-based immunotherapeutic strategies in modulating tumor immunity. The review also explores methods for rationally designing combination nanomedicine strategies to address resistance issues at multiple levels, thereby enhancing the effectiveness of NSCLC treatment. Conclusions:A deep understanding of the mechanisms of NSCLC resistance and the innovative application of nanotechnology-based delivery strategies are crucial for improving patient survival. Rationally designing combination nanomedicine strategies that target multiple resistance mechanisms simultaneously holds promise for overcoming NSCLC resistance and enhancing treatment effectiveness. Further research is needed to investigate the clinical translation of emerging nanotechnologies, providing more effective treatment strategies for NSCLC patients.

Background:Lung cancer (LC) is the most common malignant tumor in the world, and lung adenocarcinoma (LUAD) is the most common type of LC. Immune microenvironment plays a critical role in cancer from onset to relapse. We aimed to identify an effective immune-related prediction model for assessing prognosis and predicting the relevant tumor therapeutic drugs. Methods:According to the RNA sequencing data of LUAD transcriptome in The Cancer Genome Atlas (TCGA) database and the immune-related genes obtained from IMMPORT (The Immunology Database and Analysis Portal) database, immune prognosis-related genes were screened. Weighted gene co-expression network analysis (WGCNA) identified hub genes in differentially expressed immune-related genes (DEIRGs). Least absolute shrinkage and selection operator (LASSO) Cox and ten rounds of cross-validation were used to screen core genes to establish a prognostic model, and in situ hybridization was used to verify the expression of core genes in LUAD. Then the patients from the TCGA database were divided into high-risk group and low-risk group. The survival, tumor microenvironment (TME) and immune cell infiltration of different groups were further analyzed, and the differential genes between the two groups were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) enrichment analyses. Finally, the small molecular drugs that can inhibit the prognosis of LUAD were screened by Connectivity Map (CMAP), and the therapeutic mechanism of small molecular drug oxibendazole was verified by Cell Counting Kit-8 (CCK-8) experiment. Results:A four-immunoprognosis-related gene model was established to forecast the overall survival (OS) of LUAD through LASSO Cox regression and ten rounds of cross-validation analysis. This prognostic model stratified LUAD patients into low-risk and high-risk groups. According to the findings of the survival analysis, the low-risk group had a greater OS than the high-risk group and the content of immune cells in LUAD was corrected with the survival prognosis of patients. Univariate and multivariate Cox regression also revealed that the prognostic model was an independent prognosis factor in LUAD. Five kinds of small molecular drugs which can inhibit the prognosis of LUAD were screened by CMAP. As shown by CCK-8 test, the small molecular drug "oxibendazole" can effectively inhibit the proliferation of LUAD cells. Conclusions:Based on immune-related prognostic genes, a new prognostic model for LUAD was constructed. Oxibendazole can inhibit the proliferation of LUAD cells, which provides a new idea for the treatment of LUAD.

Background:Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and accounts for about 40% of all lung cancer cases. This research aims to investigate the effects of miR-9-3p on ferroptosis in LUAD cells and to elucidate its regulatory mechanisms. Studies have shown that LUAD is related to ferroptosis, and specific microRNAs (miRNA) are also related to ferroptosis. However, further research is needed to elucidate the mechanisms by which miR-9-3p induces ferroptosis in LUAD. Methods:Our study comprehensively analyzed multiple databases to investigate miR-9-3p expression in LUAD tissues. Quantitative polymerase chain reaction (qPCR) was utilized to detect miR-9-3p levels in LUAD cells and tissues, examining its prognostic significance. Reactive oxygen species (ROS) and superoxide dismutase (SOD) assays assessed the impact of miR-9-3p on lipid peroxidation in LUAD cells. Dual-luciferase reporter assays were conducted to evaluate the binding affinity between miR-9-3p and target genes, while Western blotting and immunofluorescence were used to examine the regulation of miR-9-3p on downstream signaling pathways. Results:We observed that miR-9-3p was upregulated in LUAD cells by qPCR, and the ferroptosis of LUAD cells increased upon treatment with erastin following the transfection of miR-9-3p inhibitor. Cell Counting Kit-8 (CCK-8), ROS, and SOD activity assays confirmed that inhibiting miR-9-3p enhanced lipid peroxidation in LUAD cells, contributing to higher rates of ferroptosis. Subsequent dual-luciferase reporter assays validated spermidine/spermine N1-acetyltransferase 1 (SAT1) as a target gene of miR-9-3p. Further Western blot confirmed that miR-9-3p regulated the expression of SAT1 and p53 proteins in p53 wild-type (WT) LUAD cells. Rescue experiments demonstrated that SAT1 was necessary for miR-9-3p to promote cell proliferation and suppress ferroptosis in p53 WT LUAD cells. Additionally, the effect of miR-9-3p on ferroptosis in LUAD cells was regulated by p53 signaling pathway. Conclusions:Overall, these findings demonstrate that miR-9-3p negatively regulates ferroptosis in LUAD cells through SAT1 and p53 signaling pathway, suggesting that miR-9-3p plays a crucial role in LUAD pathogenesis and targeting this miRNA with an inhibitor exhibits promising potential for the treatment of LUAD.

INTRODUCTION:The treatment of burn wounds, especially deep burn wounds, remains a major clinical challenge. Growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) show great potential in promoting the healing of damaged tissues. This study explored wound healing following targeted delivery of bFGF and VEGFA genes into deep burn wounds through a novel platelet membrane-coated nanoparticle (PM@gene-NP) complex delivery system.METHODS:First, bFGF and VEGFA genes were inserted into plasmid (pEGFP-N1) vectors. Subsequently, the assembled plasmids were loaded onto nanoparticles to form gene-loaded nanoparticle complexes, which were then wrapped with extracted platelet membrane, fully simulating the characteristics of platelets, in order to actively target sites of inflammatory damage. After administration of PM@gene-NP complexes through the tail vein of rats, a series of experiments were conducted to evaluate wound healing.RESULTS:The PM@gene-NP complexes effectively targeted the burn sites. After the administration of the PM@gene-NP complexes, the rats exhibited increased blood flow in the burn wounds, which also healed faster than control groups. Histological results showed fewer inflammatory cells in the burned skin tissue after treatment. After the wounds healed, the production of hair follicles, sebaceous glands and other skin accessories in the skin tissue increased.CONCLUSION:Our results showed that the PM@gene-NP complexes can effectively deliver gene therapy to the injured area, and this delivery system should be considered as a potential method for treating deep burns.

Lung cancer is the leading cause of cancer-related deaths worldwide. Here, the goal of our study was to explore novel biomarkers for lung adenocarcinoma (LUAD). First, we analyzed through TCGA database and GSE72904 and GSE68465 datasets by bioinformatics methods to screen potential novel biomarkers. In this study, genes with potential prognostic value were identified by constructing a prognostic model, and risk score formulas were established by minimum absolute shrinkage and selection operator (LASSO) model, multi-factor Cox regression analysis integration factor screening to obtain gene expression values for four genes (PLK1, OIP5, KRT6A, RRM2). Based on the median value of risk scores in the TCGA cohort, we identified two risk subtypes for LUAD patients: high-risk subtype, and low-risk subtype. Among them, the risk status map and the survival distribution map demonstrated that LUAD patients with higher risk score had a poorer prognosis. Further analysis by immune cell analysis and correlation analysis showed that the low-risk subtype group may benefit more from immunotherapy. In addition, we estimated the IC50 for several common drugs and found the best sensitivity to drugs in the high-risk subtypes. In conclusion, the prediction model provides a robust profile for predicting changes in prognosis in patients with LUAD. Thus, it appears to be a potentially useful prognostic tool.

Background:Calcific aortic valve disease (CAVD) is a common cardiovascular disease with high morbidity and mortality, and no effective prevention or treatment is available. In recent years, increasing evidence has shown that noncoding RNAs (ncRNAs) play an important role in the pathogenesis and prognosis of CAVD. Several associated circular RNAs (circRNAs) have been reported to be involved in CAVD, such as circRIC3 and TGFBR2. However, the limited number of circRNAs identified in CAVD warrants further in-depth investigation, and the comprehensive elucidation of their role in the key mechanisms of this disease is needed.Methods:The expression of circRNAs and microRNAs (miRNAs) were analyzed by RNA sequencing. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the expression of circRNA ARHGAP10 (circARHGAP10), miR-335-3p, and RUNX2. Luciferase reporter assay, pull-down assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to evaluate the binding of miR-335-3p to circARHGAP10 or RUNX2. Alizarin red S staining showed the formation of calcified nodules in valve interstitial cells (VICs). The expression of circARHGAP10 and miR-335-3p was altered through lentivirus infection. Alkaline phosphatase (ALP) activity was used to verify the correlation between circARHGAP10 and miR-335-3p. The expression of proteins was assessed via Western blot. RNA fluorescence in situ hybridization (FISH) was used to confirm the localization of circARHGAP10 in the cytoplasm of VICs. Immunofluorescence was used to detect the expression level of RUNX2. ApoE-/- mice were used to construct a CAVD model, circARHGAP10 short hairpin RNA (shRNA) and miR-335-3p inhibitor lentivirus were intraperitoneally injected, and scramble and inhibitor normal control (NC) lentivirus were injected as controls, followed by hematoxylin and eosin (HE) staining.Results:Through RNA sequencing, we found that circARHGAP10 (hsa_circ_0008975) was highly expressed in calcific aortic valves. CircARHGAP10 knockdown effectively inhibited the extent of osteogenic differentiation of VICs. We then found that circARHGAP10 was a competing endogenous RNA (ceRNA) of miR-355-3p and that miR-355-3p targeted RUNX2. In vitro experiments confirmed that circARHGAP10 regulated the osteogenic differentiation of VICs through the miR-355-3p/RUNX2 pathway, and this was validated in vivo using an ApoE-/- mouse model.Conclusions:These findings provide a foundation for circRNA-directed diagnostics and therapeutics for CAVD.

Introduction: The International Association for the Study of Lung Cancer (IASLC) newly proposed grading system for lung adenocarcinomas (ADC) has been shown to be of prognostic significance. Hence, intraoperative consultation for the grading system was important regarding the surgical decision-making. Here, we evaluated the accuracy and interobserver agreement for IASLC grading system on frozen section (FS), and further inves-tigated the prognostic performance.Methods: FS and final pathology (FP) slides were reviewed by three pathologists for tumor grading in 373 stage I lung ADC following surgical resection from January to June 2013 (retrospective cohort). A prospective multi-center cohort (January to June 2021, n = 212) were included to confirm the results.Results: The overall concordance rates between FS and FP were 79.1% (kappa = 0.650) and 89.6% (kappa = 0.729) with substantial agreement in retrospective and prospective cohorts, respectively. Presence of complex gland was the only independent predictor of discrepancy between FS and FP (presence versus. absence: odds ratio, 2.193; P = 0.015). The interobserver agreement for IASLC grading system on FS among three pathologists were satisfactory (kappa = 0.672 for retrospective cohort; kappa = 0.752 for prospective cohort). Moreover, the IASLC grading system by FS diagnosis could well predict recurrence-free survival and overall survival for patients with stage I invasive lung ADC.Conclusions: Our results suggest that FS had high diagnostic accuracy and satisfactory interobserver agreement for IASLC grading system. Future prospective studies are merited to validate the feasibility of using FS to match patients into appropriate surgical type.

Background. Non-small-cell lung cancer (NSCLC) is a major component of lung cancer and is significantly correlated with poor prognosis. N6-methyladenosine (m6A) RNA methylation is closely related to the occurrence, progression, and prognosis of cancer. The potential biological functions and mechanisms of m6A RNA methylation in the immune microenvironment are still unclear. Methods. We assessed m6A RNA methylation modification patterns in 1326 NSCLC patient samples based on 20 m6A regulators, linking these clusters to the tumor microenvironment and immune cell infiltration. The m6Ascore was created to quantify the m6A modification patterns of individual tumors. We then assessed the value of NSCLC patients in terms of clinical prognosis and immunotherapy response. Results. According to different mRNA expression levels, two different m6A clusters were identified. m6A aggregation was significantly associated with clinical prognostic characteristics, the tumor microenvironment, and immune-related biological processes. Fifteen differential genes were screened based on these two m6A clusters, and to further investigate the mechanisms of action of these differential genes, they were subjected to unsupervised clustering analysis, which classified them into four different genomic isoforms. Prognostic analysis indicated that the survival advantage of the m6A gene cluster A modification mode was significantly prominent. We continued to construct the m6Ascore, which was used as a scoring tool to evaluate tumor typing, immunity, and prognosis. Patients with a low m6Ascore showed a significant survival advantage, and the group with a low m6Ascore had a better prognosis predicted by immunotherapy. The anti-PD-1/L1 immunotherapy cohort showed that a lower m6Ascore was associated with higher efficacy of immunotherapy. Conclusions. The results suggest that m6A RNA methylation regulators make an important difference in the tumor immune microenvironment of patients with NSCLC. m6A gene characterization and the construction of the m6Ascore provide us with a richer understanding of m6A RNA methylation modification patterns in NSCLC patients and help to predict clinical prognosis and immunotherapeutic response.

目的 探讨三维重建结合手术教学法在胸外科实习教学中的应用效果.方法 选取2019年6月—2020年5月在南通大学附属医院胸外科实习的103名南通大学临床医学专业实习生为研究对象,随机分为试验组(n=52)和对照组(n=51).试验组采用三维重建结合手术教学法,对照组采用传统教学法.实习结束后分别对两组实习生进行理论考试、技能考试和问卷调查,其中技能考试包括影像学判读、接诊患者、临床思维和基本操作技能四部分.结果 试验组出科理论考试成绩为(95.42±1.73)分,高于对照组的(91.45±4.68)分;试验组技能考试成绩总分为(81.40±6.27),高于对照组的(78.55±5.15)分,且试验组影像学判读、接诊患者、临床思维和基本操作技能四部分成绩均高于对照组;试验组调查问卷总分为(98.29±1.12),高于对照组的(88.37±1.37)分,且试验组学习兴趣、学习主观能动性、学习效果和满意度等四方面评分均高于对照组,差异均具有统计学意义(P<0.05).结论 三维重建结合手术教学法在胸外科实习教学中应用效果明显,是一种可以提高实习生临床实习兴趣和学习效率的教学模式.

The development of calcific aortic valve disease (CAVD) is a complex process of ectopic calcification involving various factors that lead to aortic valve stenosis, hemodynamic changes, and, in severe cases, even sudden death. Currently, aortic valve replacement is the only effective method. The osteogenic differentiation of aortic valve interstitial cells (AVICs) is one of the key factors of valve calcification. Emerging evidence suggests that bone morphogenetic protein 2 (BMP2) can induce the proosteogenic activation of AVICs. However, the regulatory mechanism underlying this activation in AVICs is unclear. In the present study, we elucidated through high-throughput RNA sequencing and RT-qPCR that miR-664a-3p was evidently downregulated in the calcific aortic valve. We also proved that miR-664a-3p was involved in regulating osteogenic differentiation in AVICs. Target prediction analysis and dual-luciferase reporter gene assay confirmed that miR-664a-3p is preferentially bound to BMP2. Furthermore, the effect of the miR-664a-3p/BMP2 axis on osteogenic differentiation in AVICs was examined using the gain- and loss-of-function approach. Finally, we constructed a mouse CAVD model and verified the effect of the miR-664a-3p/BMP2 axis on the aortic valve calcification leaflets in vivo. In conclusion, miR-664a-3p regulates osteogenic differentiation in AVICs through negative regulation of BMP2, highlighting that miR-664a-3p may be a potential therapeutic target for CAVD.

BackgroundNon-small cell lung cancer (NSCLC) is a highly heterogeneous malignancy with an extremely high mortality rate. Necroptosis is a programmed cell death mode mediated by three major mediators, RIPK1, RIPK3, and MLKL, and has been shown to play a role in various cancers. To date, the effect of necroptosis on NSCLC remains unclear. MethodsIn The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we downloaded transcriptomes of lung adenocarcinoma (LUAD) patients and their corresponding clinicopathological parameters. We performed multi-omics analysis using consensus clustering based on the expression levels of 40 necroptosis-related genes. We constructed prognostic risk models and used the receiver operating characteristic (ROC) curves, nomograms, and survival analysis to evaluate prognostic models. ResultsWith the use of consensus clustering analysis, two distinct subtypes of necroptosis were identified based on different mRNA expression levels, and cluster B was found to have a better survival advantage. Correlation results showed that necroptosis was significantly linked with clinical features, overall survival (OS) rate, and immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis confirmed that these differential genes were valuable in various cellular and biological functions and were significantly enriched in various pathways such as the P53 signaling pathway and cell cycle. We further identified three genomic subtypes and found that gene cluster B patients had better prognostic value. Multivariate Cox analysis identified the 14 best prognostic genes for constructing prognostic risk models. The high-risk group was found to have a poor prognosis. The construction of nomograms and ROC curves showed stable validity in prognostic prediction. There were also significant differences in tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity between the two risk groups. The results demonstrate that the 14 genes constructed in this prognostic risk model were used as tumor prognostic biomarkers to guide immunotherapy and chemotherapy. Finally, we used qRT-PCR to validate the genes involved in the signature. ConclusionThis study promotes our new understanding of necroptosis in the tumor microenvironment of NSCLC, mines prognostic biomarkers, and provides a potential value for guiding immunotherapy and chemotherapy.

We retrospectively analyzed risk factors on in-hospital mortality in CRRT-therapy patients with open cardiac surgery (CS)-induced acute kidney injury (AKI), to provide the clinical basis for predicting and lowering the in-hospital mortality after CS. 84 CS-AKI patients with CRRT were divided into survival and death groups according to discharge status, and the perioperative data were analyzed with R version 4.0.2. There were significant differences between the two groups, including: urea nitrogen, Sequential Organ Failure Assessment (SOFA) score and vasoactive-inotropic score (VIS) on the first day after operation; VIS just before CRRT; SOFA score and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, severe infection and MODS after operation; and the interval between AKI and CRRT. Univariate logistic regression analysis showed that SOFA score and VIS on the first day after operation; VIS just before CRRT; VIS and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, infection and multiple organ dysfunction syndrome (MODS) after operation; bootstrap resampling analysis showed that SOFA score and VIS 24 h after CRRT, as well as the incidence of bleeding after operation were the independent risk factors. Maintaining stable hemodynamics and active prevention of bleeding are expected to decrease the in-hospital mortality.

Cancer-associated fibroblasts (CAFs) are the most important stromal cells in the tumor microenvironment (TEM) and have been reported to regulate various cancer development. Exosomes are considered important elements involved in intercellular communication and TME regulation, while the potential function of CAFs in lung cancer immunosuppressive microenvironments remains unknown. CAFs-derived exosomes (CAFs-exo) and normal fibroblasts (NFs)-derived exosomes (NFs-exo) were isolated by ultra-centrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot analysis. A549 cells were co-cultured with peripheral blood mononuclear cells (PBMCs). Flow cytometry assay was performed to detect the killing role of PBMCs on A549 cells. Bioinformatics and luciferase reporter assays were used to analyze the relationship among microRNA (miRNA), long non-coding RNA (lncRNA) and target gene. BALB/c mice were used to construct the lung cancer model by subcutaneous injection. Programmed death ligand 1 (PD-L1) was up-regulated in lung cancer tissues and cells. PD-L1 also up-regulated in CAFs cell medium-mediated A549 cells. CAFs decreased PBMCs induced-cell apoptosis through increasing PD-L1 in A549 cells. Moreover, CAFs transferred exosomes to lung cancer cells to suppress the killing effect of PBMCs through up-regulating PD-L1. Using microarray assays, opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) level was highly expressed in CAFs-exos. After treatment by CAFs-exos, miR-142-5p level was significantly down-regulated in A549 cells. OIP5-AS1 served as a sponge to target miR-142-5p and negatively regulated miR-142-5p expression in lung cancer cells. In addition, PD-L1 was a direct target of miR-142-5p. CAFs derived exosomal OIP5-AS1 reduced PBMCs induced-cell apoptosis and promoted tumor growth through decreasing miR-142-5p and up-regulating PD-L1. CAFs-derived exosomes suppressed the role of PBMCs induced-killing of lung cancer cells and promoted lung cancer progression by OIP5-AS1/ miR-142-5p/ PD-L1 axis, which provided a potential opportunity for diagnosis and treatment of lung cancer.

INTRODUCTION:The aim of the study was to investigate the clinical significance of Ly-1 antibody reactive clone (LYAR) in non-small-cell lung cancer (NSCLC).MATERIAL AND METHODS:The expressions of LYAR at the protein level in representative paired NSCLC tumor tissues and adjacent non-tumor tissues were measured by Western blot and immunohistochemistry. Kaplan-Meier method was used to calculate the survival curve of patients with NSCLC. Cell Counting Kit-8 assay and flow cytometry were used to estimate the cell proliferation and cell cycle, respectively. Terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect cell apoptosis.RESULTS:LYAR was dramatically overexpressed in NSCLC tissues which were closely related to the survival of patients with NSCLC. In clinical studies, the expression of LYAR was related to the clinical stage, histological differentiation, and Ki-67 expression. A positive correlation was found between LYAR and Ki-67 expression by Spearman's correlation test. After serum starvation for 72 h, serum re-addition significantly increased the expression of LYAR, PCNA, and Cyclin A and promoted the cell cycle progression. LYAR knockdown inhibited the proliferation and induced the G0/G1 cell cycle arrest and apoptosis of A549 cells.CONCLUSIONS:The present study revealed the clinical significance of LYAR in NSCLC. LYAR might serve as a tumor promoter in NSCLC progression by promoting the proliferation and inhibiting the apoptosis of NSCLC cells. Inhibiting the expression of LYAR was considered as a potential novel therapeutic strategy for NSCLC.