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Hua-Xi Zou,1,2,* Tie Hu,1,2,* Jia-Yi Zhao,2,3,* Bai-Quan Qiu,2,4 Chen-Chao Zou,2,4 Qi-Rong Xu,1 Ji-Chun Liu,1,2 Song-Qing Lai,1,2 Huang Huang1,2 1Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Medical Innovation Experimental Program, Huan Kui College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huang Huang; Song-Qing Lai, Email jack19871212@hotmail.com; ndyfy03743@ncu.edu.cnIntroduction: Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart.Methods: We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes.Results: We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs.Conclusion: This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.Keywords: septic myocardial injury, ferroptosis, heart transcriptome, key genes, database

Li-Jun Wang,1,* Bai-Quan Qiu,1,* Ming-Ming Yuan,2,* Hua-Xi Zou,1 Cheng-Wu Gong,1 Huang Huang,2 Song-Qing Lai,3 Ji-Chun Liu1 1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Chun Liu, Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13907913502, Email liujichun999@yeah.net Song-Qing Lai, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13699562160, Email ndyfy03743@ncu.edu.cnPurpose: Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA–mRNA pairs and drugs related to DCM.Methods: The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA–mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed.Results: In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4, and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified.Conclusion: In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.Keywords: dilated cardiomyopathy, miRNA, mRNA, public database, drugs

Background: Neuropathic pain (NP) is a debilitating condition caused by lesion or dysfunction in the somatosensory nervous system. Accumulation of advanced oxidation protein products (AOPPs) is implicated in mechanical hyperalgesia. However, the effects of AOPPs on NP remain unclear., Methods: A rat model of NP was established by chronic constriction injury (CCI) and employed to evaluate the changes of mechanical withdrawal threshold, thermal and cold withdrawal latency, as well as AOPPs levels. The effects of AOPPs on the activation of satellite glial cells (SGCs) in the dorsal root ganglion (DRG), receptor for advanced glycation end-products (RAGE) expression, and NF-κB signaling pathway activation were also investigated using western blotting, immunofluorescence, and the Fluo4-AM fluorescence probe for calcium signaling. Additionally, oxidative stress levels and inflammatory cytokine production in SGCs, triggered by AOPPs exposure, were measured through the DCFH-DA probe for ROS detection and ELISA kits for cytokine quantification., Results: CCI significantly elevated the AOPPs levels in the plasma and sciatic nerve and caused AOPPs accumulation in the DRG. Exogenous AOPPs activated SGCs, increased reactive oxygen species and inflammatory response, upregulated the RAGE, and activated NF-κB signaling. The RAGE inhibitor FPS-ZM1 effectively inhibited AOPPs-induced SGC activation. Additionally, AOPPs intervention worsened CCI-induced hyperalgesia and neuroinflammation in vivo., Conclusion: These results indicate that AOPPs exacerbate the SGC activation and NP following nerve injury, and AOPPs accumulation might play an important role in the pathogenesis of NP., Competing Interests: Declarations. Ethics approval and consent to participate: This study was adhered to the guidelines of the International Association for the Study of Pain. Approval was granted by the Experimental Animal Care and Use Committee of Nanfang Hospital, Southern Medical University (NFYY-2022-0322). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiac disorder characterized by ventricular hypertrophy resulting from the disordered arrangement of myocardial cells, which leads to impaired cardiac function or death. Autophagy (AT) is a biochemical process through which lysosomes degrade and recycle damaged or discarded intracellular components to protect cells against external environmental conditions, such as hypoxia and oxidative stress. AT is closely related to HCM, and thus, serves an important role in myocardial hypertrophy. However, the precise mechanism underlying the regulation of AT in cardiac hypertrophy remains elusive. The present study aimed to examine the role and mechanisms of AT-related genes (ARGs) in HCM through bioinformatics analysis and experimental validation and to identify potential targeted drugs for HCM. In this study, cardiac samples were obtained from healthy individuals and patients with HCM from the GEO database, and screened for differentially expressed ARGs to further investigate their potential interactions and functional pathways. These genes were subjected to functional enrichment analysis to identify potential crosstalk and involved pathways. Based on a protein-protein interaction network, EIF4EBP1, MCL1, PIK3R1, CCND1 and PPARG were identified as potential biomarkers for the diagnosis and treatment of HCM. Furthermore, 10 components with therapeutic potential for HCM were predicted based on the aforementioned hub genes. The results of bioinformatics analysis were validated using H9c2 cells stimulated with angiotensin II, which represented an in vitro model of cardiac hypertrophy. Overall, the present study demonstrated that the expression levels of ARGs were substantially altered in HCM. Therefore, these genes may be used as diagnostic biomarkers and therapeutic targets for HCM., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Qiu et al.)

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. β-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women., Competing Interests: Declaration of competing interest The authors assert that the research was carried out without any commercial or financial associations that could be interpreted as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study aimed to explore how resveratrol (Res) confers myocardial protection by attenuating ferroptosis. In vivo and in vitro myocardial ischemia/reperfusion injury (MIRI) models were established, with or without Res pretreatment. The results showed that Res pretreatment effectively attenuated MIRI, as evidenced by increased cell viability, reduced lactate dehydrogenase activity, decreased infarct size, and maintained cardiac function. Moreover, Res pretreatment inhibited MIRI-induced ferroptosis, as shown by improved mitochondrial integrity, increased glutathione level, decreased prostaglandin-endoperoxide synthase 2 level, inhibited iron overload, and abnormal lipid peroxidation. Of note, Res pretreatment decreased or increased voltage-dependent anion channel 1/glutathione peroxidase 4 (VDAC1/GPX4) expression, which was increased or decreased via anoxia/reoxygenation (A/R) treatment, respectively. However, the overexpression of VDAC1 via pAd/VDAC1 and knockdown of GPX4 through Si-GPX4 reversed the protective effect of Res in A/R-induced H9c2 cells, whereas the inhibition of GPX4 with RSL3 abolished the protective effect of Res on mice treated with ischemia/reperfusion.Interestingly, knockdown of VDAC1 by Si-VDAC1 promoted the protective effect of Res on A/R-induced H9c2 cells and the regulation of GPX4. Finally, the direct interaction between VDAC1 and GPX4 was determined using co-immunoprecipitation. In conclusion, Res pretreatment could protect the myocardium against MIRI-induced ferroptosis via the VDAC1/GPX4 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this study., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts., (© 2024 Wiley Periodicals LLC.)

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Zhao et al.)

Tanshinone IIA (TSN) extracted from danshen ( Salvia miltiorrhiza ) could protect cardiomyocytes against myocardial ischemia/reperfusion injury (IRI), however the underlying molecular mechanisms of action remain unclear. The aim of the present study was to identify the protective effects of TSN and its mechanisms of action through in vitro studies. An anoxia/reoxygenation (A/R) injury model was established using H9c2 cells to simulate myocardial IRI in vitro . Before A/R, H9c2 cardiomyoblasts were pretreated with 8 µM TSN or 10 µM ferrostatin‑1 (Fer‑1) or erastin. The cell counting kit 8 (CCK‑8) and lactate dehydrogenase (LDH) assay kit were used to detect the cell viability and cytotoxicity. The levels of total iron, glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), ferrous iron, caspase‑3 activity, and reactive oxygen species (ROS) were assessed using commercial kit. The levels of mitochondrial membrane potential (MMP), lipid ROS, cell apoptosis, and mitochondrial permeability transition pore (mPTP) opening were detected by flow cytometry. Transmission electron microscopy (TEM) was used to observed the mitochondrial damage. Protein levels were detected by western blot analysis. The interaction between TSN and voltage‑dependent anion channel 1 (VDAC1) was evaluated by molecular docking simulation. The results showed that pretreatment with TSN and Fer‑1 significantly decreased cell viability, glutathione peroxidase 4 (GPX4) protein and GSH expression and GSH/GSSG ratio and inhibited upregulation of LDH activity, prostaglandin endoperoxide synthase 2 and VDAC1 protein expression, ROS levels, mitochondrial injury and GSSG induced by A/R. TSN also effectively inhibited the damaging effects of erastin treatment. Additionally, TSN increased MMP and Bcl‑2/Bax ratio, while decreasing levels of apoptotic cells, activating Caspase‑3 and closing the mPTP. These effects were blocked by VDAC1 overexpression and the results of molecular docking simulation studies revealed a direct interaction between TSN and VDAC1. In conclusion, TSN pretreatment effectively attenuated H9c2 cardiomyocyte damage in an A/R injury model and VDAC1‑mediated ferroptosis and apoptosis served a vital role in the protective effects of TSN.

Acute myocardial infarction is a life-threatening condition with high mortality and complication rates. Although myocardial reperfusion can preserve ischemic myocardial tissue, it frequently exacerbates tissue injury, a phenomenon known as ischemia-reperfusion injury (IRI). However, the underlying pathological mechanisms of IRI remain to be completely understood. Ferroptosis is a novel type of regulated cell death that is associated with various pathological conditions, including angiocardiopathy. The purpose of this article was to elucidate the possible mechanistic role of ferroptosis in IRI through bioinformatics analysis and experimental validation. Healthy and IRI heart samples were screened for differentially expressed ferroptosis-related genes and functional enrichment analysis was performed to determine the potential crosstalk and pathways involved. A protein-protein interaction network was established for IRI, and 10 hub genes that regulate ferroptosis, including HIF1A , EGFR , HMOX1 , and ATF3 were identified. In vitro, an anoxia/reoxygenation (A/R) injury model was established using H9c2 cardiomyoblasts to validate the bioinformatics analysis results, and extensive ferroptosis was detected. A total of 4 key hub genes and 3 key miRNAs were also validated. It was found that IRI was related to the aberrant infiltration of immune cells and the small-molecule drugs that may protect against IRI by preventing ferroptosis were identified. These results provide novel insights into the role of ferroptosis in IRI, which can help identify novel therapeutic targets., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Hu et al.)

Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein-protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zou, Qiu, Zhang, Hu, Wan, Liu, Huang and Lai.)

Septic cardiomyopathy (SCM) is a cardiac dysfunction caused by severe sepsis and septic shock that increases the risk of heart failure and death and its molecular mechanism remains unclear. Ferroptosis, a novel form of programmed cell death, has been reported to be present in the heart tissue of patients with sepsis, which demonstrated that ferroptosis may be a potential mechanism of myocardial injury in SCM. Therefore, we explored the role of ferroptosis-related genes (FRGs) in SCM and aimed to identify pivotal ferroptosis-related targets in SCM and potential therapeutic targets involved in the pathological process of SCM. To explore the regulatory mechanisms of ferroptosis in SCM, we identified differentially expressed genes (DEGs) in SCM and FRGs by bioinformatics analysis, and further identified hub genes. And the crucial microRNAs (miRNAs)-FRGs regulatory network was subsequently constructed. Finally, several candidate drugs associated with the hub genes were predicted, and Real-time quantitative reverse Transcription PCR (qRT-PCR) and western blotting analysis were performed to confirm the abnormal expression of hub genes. In this study, we identified several FRGs that may be involved in the pathogenesis of SCM, which helps us further clarify the role of ferroptosis in SCM and deeply understand the molecular mechanisms and potential therapeutic targets of SCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Yuan, Qiu, Wang, Zou, Hu, Lai and Liu.)

Background: Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study., Methods: Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells., Results: We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes., Conclusion: Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma., (© 2021. The Author(s).)

Stanford type A aortic dissection (TAAD) is one of the most dangerous vascular diseases worldwide, and the mechanisms of its development remain unclear. Further molecular pathology studies may contribute to a comprehensive understanding of TAAD and provide new insights into diagnostic markers and potential therapeutic targets. Recent studies have identified that ferroptosis, a form of cell death, may play a previously unrecognized role in influencing the development of TAAD. In this study, we explored the pathological role of ferroptosis in TAAD by performing bioinformatics analyses. Gene set enrichment analysis (GSEA) showed that the ferroptosis-related gene (FRG) set was significantly different between normal and TAAD aortic samples at an overall level ( p < 0.001). Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses explored the potential functions and pathways of FRG in TAAD. We further identified six key genes (CA9, HMOX1, IL6, CDKN1A, HIF1A, MYC) from differentially expressed FRGs in TAAD by constructing a protein-protein interaction (PPI) network, all key genes were upregulated in TAAD. Four of the key genes (CA9, IL6, CDKN1A, and HIF1A) were demonstrated to be correlated with cigarette smoke extract-induced ferroptosis in aortic vascular smooth muscle cells. These results suggest that ferroptosis is one of the essential pathological processes in the development of TAAD, and some FRGs affect TAAD development by mediating cellular ferroptosis, which provides deepening insights into the molecular mechanisms and potential therapeutic targets of TAAD.

Aortic dissection (AD) is a catastrophic cardiovascular emergency with a poor prognosis, and little preceding symptoms. Abnormal lipid metabolism is closely related to the pathogenesis of AD. However, comprehensive lipid alterations related to AD pathogenesis remain unclear. Moreover, there is an urgent need for new or better biomarkers for improved risk assessment and surveillance of AD. Therefore, an untargeted lipidomic approach based on ultra-high-performance liquid chromatograph-mass spectrometry was employed to unveil plasma lipidomic alterations and potential biomarkers for AD patients in this study. We found that 278 of 439 identified lipid species were significantly altered in AD patients ( n = 35) compared to normal controls ( n = 32). Notably, most lipid species, including fatty acids, acylcarnitines, cholesteryl ester, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylinositols, diacylglycerols, and triacylglycerols with total acyl chain carbon number ≥54 and/or total double bond number ≥4 were decreased, whereas phosphatidylethanolamines and triacylglycerols with total double bond number <4 accumulated in AD patients. Besides, the length and unsaturation of acyl chains in triacylglycerols and unsaturation of 1-acyl chain in phosphatidylethanolamines were decreased in AD patients. Moreover, lysophosphatidylcholines were the lipids with the largest alterations, at the center of correlation networks of lipid alterations, and had excellent performances in identifying AD patients. The area under the curve of 1.0 and accuracy rate of 100% could be easily obtained by lysophosphatidylcholine (20:0/0:0) or its combination with lysophosphatidylcholine (17:0/0:0) or lysophosphatidylcholine (20:1/0:0). This study provides novel and comprehensive plasma lipidomic signatures of AD patients, identifies lysophosphatidylcholines as excellent potential biomarkers, and would be beneficial to the pathogenetic study, risk assessment and timely diagnosis and treatment of AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Ye, Lai, Zou, Yuan, Wu, Wan, Wang, Zhou, Wang, Cao, Huang, Chen, Yang and Liu.)

Idiopathic pulmonary arterial hypertension (IPAH) is a rare vascular disease with a poor prognosis, and the mechanism of its development remains unclear. Further molecular pathology studies may contribute to a comprehensive understanding of IPAH and provide new insights into diagnostic markers and potential therapeutic targets. Iron deficiency has been reported in 43-63% of patients with IPAH and is associated with reduced exercise capacity and higher mortality, suggesting that dysregulated iron metabolism may play an unrecognized role in influencing the development of IPAH. In this study, we explored the regulatory mechanisms of iron metabolism in IPAH by bioinformatic analysis. The molecular function of iron metabolism-related genes (IMRGs) is mainly enriched in active transmembrane transporter activity, and they mainly affect the biological process of response to oxidative stress. Ferroptosis and fluid shear stress and atherosclerosis pathways may be the critical pathways regulating iron metabolism in IPAH. We further identified 7 key genes (BCL2, GCLM, MSMO1, SLC7A11, SRXN1, TSPAN5, and TXNRD1) and 5 of the key genes (BCL2, MSMO1, SLC7A11, TSPAN5, and TXNRD1) as target genes may be regulated by 6 dysregulated miRNAs (miR-483-5p, miR-27a-3p, miR-27b-3p, miR-26b-5p, miR-199a-5p, and miR-23b-3p) in IPAH. In addition, we predicted potential IPAH drugs-celastrol and cinnamaldehyde-that target iron metabolism based on our results. These results provide insights for further definition of the role of dysregulated iron metabolism in IPAH and contribute to a deeper understanding of the molecular mechanisms and potential therapeutic targets of IPAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hua-Xi Zou et al.)

A tunable photocatalytic method is reported for anti-Markovnikov hydro- and aminooxygenation of unactivated alkenes using readily accessible ketoxime carbonates as the diverse functionalization reagents. Mechanistic studies reveal that this reaction is initiated through an energy-transfer-promoted N-O bond homolysis of ketoxime carbonates leading to alkoxylcarbonyloxyl and iminyl radicals under visible-light photocatalysis, followed by the addition of alkoxylcarbonyloxyl radical to alkenes. By taking advantage of the different stability of the iminyl radicals, the generated carbon radical either abstracts a hydrogen atom from the media to form the anti-Markovnikov hydrooxygenation product, or it is trapped by the persistent iminyl radical to furnish the aminooxygenation product. Notably, this is the first example of direct hydrooxygenation of unactivated olefins with anti-Markovnikov regioselectivity involving an oxygen-centered radical., (© 2021 Wiley-VCH GmbH.)

This work represents the first [4+2] annulation of hydroxamic acids with olefins for the synthesis of benzo[c][1,2]oxazines scaffold via anode-selective electrochemical oxidation. This protocol features mild conditions, is oxidant free, shows high regioselectivity and stereoselectivity, broad substrate scope of both alkenes and hydroxamic acids, and is compatible with terpenes, peptides, and steroids. Significantly, the dioxygenation of olefins employing hydroxamic acid is also successfully achieved by switching the anode material under the same reaction conditions. The study not only reveals a new reactivity of hydroxamic acids and its first application in electrosynthesis but also provides a successful example of anode material-tuned product selectivity., (© 2020 Wiley-VCH GmbH.)

Both the Notch1 and Keap1-Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1-Nrf2 crosstalk in myocardial ischemia-reperfusion injury is unclear. In this study, we established hypoxia-reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1-Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1-Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1-Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.

Background: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20-39 years old., Methods: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity., Results: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m 2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m 2 (aOR = 3.68, p = 0.044)., Conclusion: SSB consumption is significantly associated with low serum testosterone in men 20-39 years old in the United States.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Elucidation of the pathogenesis and biology of lung cancer is critical for the design of an effective treatment for patients. Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases. The abnormal expression of Notch signaling pathway members is a relatively frequent event in NSCLC. The Notch signaling pathway serves important roles in cell fate determination, proliferation, differentiation and apoptosis. Increasing evidence supports the association of Notch signaling dysregulation with various types of malignant tumor, including NSCLC. Several studies have demonstrated that members of the Notch signaling pathway may be potential biomarkers for predicting the progression and prognosis of patients with NSCLC. Furthermore, Notch signaling serves critical roles in the tumorigenesis and treatment resistance of NSCLC cells by promoting the proliferation or inhibiting the apoptosis of NSCLC cells. The present review provides a detailed summary of the roles of Notch signaling in NSCLC.

Objective: To investigate the correlation between liver and skeletal muscle fat contents and insulin resistance in obese individuals with different levels of glucose tolerance., Methods: RESULTS: Ten non-obese individuals with normal glucose tolerance (NGT), 9 obese individuals with NGT, and 7 obese individuals with impaired glucose tolerance (IGT) were enrolled in this study. All the participants were examined for insulin sensitivity by hyperinsulinemic-euglycemic clamp and for liver and skeletal muscle fat accumulation quantified by proton magnetic resonance spectroscopy (1H MRS). The data were collected from the subjects including somatometric measurements, fasting plasma glucose, 2-h plasma glucose (2hPG), fasting insulin, and blood biochemistry. Linear correlation analysis and multiple linear stepwise regression analysis were used to analyze the relationship between ectopic fat accumulation and insulin resistance., Results: The glucose infusion rates (GIR, presented as the M value) differed significantly among IGT-obese (3.95∓1.66 mg·kg -1 ·min -1 ), NGT-obese (6.14∓1.90 mg·kg -1 ·min -1 ) and NGT-non-obese (8.78∓2.46 mg·kg -1 ·min -1 ) groups (P<0.05). The 3 groups also showed significant differences in liver fat contents [(15.23∓3.09)%, (6.25∓0.38)%, and (1.89∓0.90)%, respectively, P<0.05] and intramyocellular lipids in the tibialis anterior (2.69∓0.95, 2.61∓1.45, and 1.54∓0.66 mmol/kg, respectively, P<0.05). Linear analysis revealed that liver fat content, but not skeletal muscle fat content, was significantly correlated with the M value. Multiple linear stepwise regression analysis using M value as the dependent variable (Y) revealed that liver fat content (X) was an independent factor inversely correlated with the M value (regression equation: Y=-30.562X+9.007, R 2 =0.717, P<0.01)., Conclusions: Liver fat accumulation, but not skeletal muscle fat accumulation, is correlated with insulin resistance and impaired glucose metabolism.

Objective: To investigate the risk factors and survival status of hypopharyngeal carcinoma with synchronous second primary carcinoma of the esophagus. Methods: One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from January 2009 to December 2012 were retrospectively reviewed. The clinical data, tumor-related information and follow-up results were collected and analyzed. Results: Forty-three synchronous esophageal carcinomas (27%) were detected in 160 patients with hypopharyngeal carcinoma, and most patients (72%) were at an early stage. On univariate analysis, the median age of less than 55 years old (χ(2)=4.525, P =0.033), excessive alcohol consumption (χ(2)=6.942, P =0.008) and invasion site more than 3 anatomical regions (χ(2)=21.503, P =0.000) had a significant correlation with the occurrence of synchronous esophageal carcinomas. Multivariate analysis showed that excessive alcohol consumption ( OR =4.787, P =0.029) and invasion site more than 3 anatomical regions ( OR =14.391, P =0.000) were independent risk factors. The median survival time was 26 months in 43 patients with synchronous esophageal carcinomas, which was significantly lower than that (58 months) in patients without secondary primary esophageal carcinomas (χ(2)=11.981, P =0.001). Conclusions: There is a high incidence of synchronous esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers, is warranted.

Background: The study assessed the effect of continuous positive airway pressure (CPAP) therapy on the risk of developing type 2 diabetes by evaluating change in the homeostasis model assessment of insulin resistance (HOMA-IR) fasting blood glucose (FBG) and fasting insulin following CPAP treatment in non-diabetic patients and pre-diabetic with obstructive sleep apnea (OSA)., Methods: Medline, PubMed, Cochrane, and EMBASE databases were searched until August 24, 2015. The analysis included randomized controlled trials (RCTs), two arm prospective studies, cohort studies, and retrospective studies. The primary outcome measure was change of HOMA-IR in pre-diabetic patients receiving CPAP treatment., Results: Twenty-three studies were included with 965 patients who had OSA. Nineteen studies were prospective studies and four were RCTs. CPAP therapy resulted in a significant reduction in the pooled standard difference in means of HOMA-IR (-0.442, P=0.001) from baseline levels compared with the control group. Change in FBG and fasting insulin from baseline levels was similar for the CPAP and control groups. For RCT studies (n=4), there was no difference in change in HOMA-IR or FBG levels from baseline between CPAP and control groups. The combined effect of RCTs showed that CPAP was associated with a significant reduction in change from baseline in fasting insulin than the control group (standardized diff. in means between groups=-0.479, P value=0.003)., Conclusion: These findings support the use of CPAP in non-diabetic and pre-diabetic patients with OSA to reduce change of HOMA-IR and possibly reduce the risk of developing type 2 diabetes in this patient population., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to explore factors affecting cardiorespiratory fitness in males and females with different body mass index (BMI)., Methods: The National Health and Nutrition Examination Survey 1999-2004 data were used for this retrospective study. Estimated maximal oxygen uptake (VO 2max ) is surrogate for cardiorespiratory fitness (CRF). Univariate and multivariate linear regression analyses were performed to explore whether study variables were associated with estimated VO 2max stratified by gender and BMI categories., Results: A total of 3292 subjects 20-49 years of age were included in the analysis. CRF significantly decreased as BMI increased in both females and males. Ethnic difference was found in normal BMI in both genders and obese females; homocysteine was significantly negatively associated with estimated VO 2max , as was total cholesterol. Obese male subjects with diabetes had a lower estimated VO 2max than those without diabetes, and C-reactive protein (CRP) level and vitamin B12 level were significantly negatively associated with CRF. Female subjects with diabetes had higher estimated VO 2max than those without diabetes. Folate was significantly positively correlated with estimated VO 2max , whereas CRP was negatively correlated in obese female., Conclusions: There are different predictors of CRF in males and females, and in individuals with different BMI. Key messages Different BMI classes are associated with different predictors of cardiorespiratory fitness. Indicators of cardiorespiratory fitness differ between sexes.

Objective: To evaluate the clinical efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and analyze the factors affecting the efficacy., Methods: Ultrasound-guided lauromacrogol sclerotherapy was performed in 97 patients with a total of 99 benign thyroid cysts. The changes in cystic volume and other thyroid parameters were evaluated at 1, 3, 6, and 12 months after sclerotherapy. According to changes in the cystic volume, the efficacy of sclerotherapy was defined as therapeutic failure (with a volume reduction <50%), treatment success (volume reduction ≥50%) and cure (volume reduction ≥90%). The factors of affecting the efficacy of sclerotherapy was analyzed using COX regression., Results: The mean cystic volume at 1, 3, 6 and 12 months after sclerotherapy were reduced from the baseline volume of 12.08∓11.56 cm 3 to 5.63∓8.51 cm 3 , 5.96∓8.42 cm 3 , 3.80∓5.50 cm 3 and 2.85∓3.98 cm 3 , respectively, with an average cystic volume reduction rate of (70.02∓33.72)%. Therapeutic success was achieved 82 of the 99 cysts (82.83%) and cure was achieved 63cysts (63.64%) at 12 months after the procedure. A second sclerotherapy was performed for 13 cysts which did not show a volume reduction at 1-3 months after the initial procedure. A disease course of over 12 months was an independent risk factor for a second sclerotherapy (23.7% [9/38] vs 6.6% [4/61], OR=4.473 [1.238-16.169], P=0.022). The efficacy of sclerotherapy was related to cystic cavity separation, cystic fluid viscosity, cystic/solid ratio and cystic wall thickness. COX regression analysis revealed that cystic cavity separation (HR=2.25, 95%CI: 1.19-4.25) and cystic fluid viscosity (HR=2.02, 95%CI: 1.19-3.43) were the major factors affecting the treatment efficacy., Conclusion: Ultrasound-guided lauromacrogol sclerotherapy is effective and safe for treatment of benign thyroid cysts, and the maximal treatment effect can be achieved at 6 months after sclerotherapy and in cases of uncomplicated cysts with non-viscous cystic fluid, no solid cystic cavity separation and a disease course of less than 12 months.

Neo-intima development and atherosclerosis limit the long-term use of vein grafts for revascularization of ischemic tissues. Recently, studies have confirmed that proliferating cell nuclear antigen (PCNA) plays an important role in cell proliferation. Our research confirmed that 28 days after vein transplantation, PCNA expression increases significantly. Using rabbits, rather than rodents, for a more representative model of human vein grafts, we aimed to establish a time course of changes in cell proliferation and apoptosis using morphometric and immunohistochemical analyses, western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling, and transmission electron microscopy (TEM). The external jugular veins of 42 healthy purebred male New Zealand white rabbits were grafted onto their common carotid arteries. The rabbits were divided into seven groups, with vein grafts being harvested before surgery, and at 1, 3, 7, 14, 28, and 90 days afterwards. The extent of stenosis and apoptosis, PCNA protein levels, and TEM morphology were subsequently examined. Intimal thickness was slightly decreased 1 day following surgery, but then increased continuously until the 90th day. Western blot and immunohistochemistry both indicated lowered PCNA expression on day 1, although levels subsequently increased, peaking at 7 days post-surgery. After surgery, apoptosis was lowest on day 7, and remained low thereafter. TEM revealed signs of apoptosis as vein graft restenosis progressed. Proliferation and apoptosis co-occurred following grafting, indicating that both processes were involved in vein graft remodeling. Apoptosis levels were highest between days 1 and 3 after surgery, whereas proliferation culminated on the 7th day.

Aims/introduction: To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes., Materials and Methods: As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study. After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks. Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group., Results: Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index. Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values. Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline., Conclusions: It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.

A Pseudomonas exotoxin (PE-KDEL)-based chimeric subunit vaccine system was recently developed using a reverse vaccinology technique. In this study, the plasmids containing PE-PRRS chimeric subunits were constructed that composed of porcine reproductive and respiratory syndrome virus (PRRSV) antigen moieties, a ligand moiety and a Pseudomonas exotoxin A deleted domain III (PE (ΔIII)), and a carboxyl terminal moiety that includes a polypeptide with amino acid sequence KDEL (K3). The PE-PRRS combination vaccine can effectively induce not only PRRSV-specific INF-γ cellular immunity but also a slow-reacting and complement-requiring type serum neutralizing antibody in pigs. In a specific pathogen free (SPF) pig challenge model, body temperature (colonic temperature), occurrence of PRRSV viremia, nasal excretions, gross and histopathological appearances of pneumonia, and serum antibody activity (IFA and SN) titers significantly differed between the immunized group and the control group. The survey showed that a 0.3mg/dose PE-PRRS vaccine formula conferred protection against PRRSV. A field trial of PE-PRRS vaccine was performed to study the immune response of pregnant sows after vaccination in a PRRSV persist farm. The RT-PCR analysis of viremia and serological titers showed that the PE-PRRS vaccine not only increased sow reproductive performance and evoked its immune response to PRRS viremia, it also activated maternal immune protections to prevent piglets from inflicting viremia. In conclusion, we developed a novel and effective PRRS cytotoxic T-cells (CTLs)-based vaccine containing Pseudomonas exotoxin (PE-KDEL) carrier in combination with PRRSV conserved epitopes against PRRS virus., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To investigate different strategies for displaying the hypopharynx and oesophageal entrance during laryngoscopy for hypopharyngeal cancer., Patients and Methods: A total of 113 patients with hypopharyngeal cancer underwent laryngoscopy prior to surgery. The hypopharynx was displayed by: (1) pulling the anterior cervical skin; (2) having the patient perform the Valsalva balloon-blowing manoeuvre; and (3) injecting oxygen through the biopsy channel to expose the oesophageal entrance. The effect of these methods on visualisation of primary tumour size and extent was assessed., Results: During pronunciation of the letter ‘e’, the hypopharynx was displayed in only 33 patients (29.2 per cent); with anterior cervical skin traction plus the balloon-blowing manoeuvre, the hypopharynx was displayed in 106 patients (93.8 per cent; p < 0.001). The combined strategy was superior especially when judging the extent of posterior pharyngeal wall and postcricoid invasion. Oesophageal entrance involvement was visible in 33 patients upon injecting oxygen through the laryngoscopic biopsy channel, and in 25 patients during radiological examination; laryngoscopy was superior to radiological examination in determining the extent of oesophageal entrance invasion (p = 0.003)., Conclusion: Adequate laryngoscopic display of the hypopharynx could increase the accuracy of pre-treatment hypopharyngeal cancer staging.

Objective: To investigate the value of narrow band imaging (NBI) endoscopy in the detection of unknown primary tumor site with cervical lymph node metastases of squamous cell carcinoma., Methods: Fifty-three patients with cervical lymph node metastases of squamous cell carcinoma treated in our department between June 2009 and December 2011 were enrolled in this study. Their primary tumor site was not detected by routine computed tomography, magnetic resonance imaging and laryngoscopy. The nasopharyngolarynx was examined by NBI endoscopy to explore the primary tumor site., Results: A total of 53 cases with cervical lymph node metastasis of squamous cell carcinoma from an unknown primary were examined under NBI endoscopy. The primary tumor site was confirmed by NBI examination in 47.2% (25/53) of patients, significantly better than routine radiology and endoscopy (0, P < 0.001). These primary tumors were small and superficial, with characteristic mucosal vascular morphologies. The superficial nasopharyngeal carcinomas under NBI examination showed the superficial thin branch-like or torturous line microvessels. The notable characteristics of the squamous cell carcinoma of oropharynx, hypopharynx and larynx was the well demarcated brownish area and scattered brown dots., Conclusion: The NBI endoscopy can provide better visualization of the morphology of superficial mucosal vasculature and improve the ability to detect possible primary cancer in patients with primary unknown cervical lymph node metastasis.

Objective: To evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion., Methods: A retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared., Results: In EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)]., Conclusions: EMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.

Objective: To investigate the method displaying the hypopharynx and esophageal entrance under laryngoscopy to determine the invasion range of hypopharyngeal cancer., Methods: A total of 113 patients with hypopharyngeal cancer was enrolled in this study and they previously underwent conventional laryngoscopic and radiologic examinations. The esophageal entrance was exposed by injecting gas through the biopsy channel of laryngoscope. The invasion of esophageal entrance in hypopharyngeal cancers was evaluated by this method and compared with that evaluated with radiology., Results: Conventional laryngoscopy was unable to evaluate appreciably esophageal entrance involvement in the 113 patients with hypopharyngeal cancer. After injecting gas through the laryngoscopic biopsy channel, the esophageal entrance was clearly displayed in 96.5% (109/113) patients, showing the presence (33 cases) and absence (76 cases) of esophageal entrance invasion. Imaging examinations only showed the invasion of the esophageal entrance in 25 patients of these patients,but did not in other 8 patients. Laryngoscopy with injecting gas through the biopsy channel was superior to radiological imaging examinations in determining the invasion of the esophageal entrance (χ² = 9.103, P = 0.003)., Conclusion: Laryngoscopy with injecting gas through the biopsy channel is a useful method for determining the presence or absence of esophageal entrance invasion in hypopharyngeal cancer prior to surgery.

Objective: To investigate the characteristics of the laryngeal mucosal microvascular network in suspected laryngeal cancer patients, using narrow band imaging, and to evaluate the value of narrow band imaging endoscopy in the early diagnosis of laryngeal precancerous and cancerous lesions., Patients and Methods: Eighty-five consecutive patients with suspected precancerous or cancerous laryngeal lesions were enrolled in the study. Endoscopic narrow band imaging findings were classified into five types (I to V) according to the features of the mucosal intraepithelial papillary capillary loops assessed., Results: A total of 104 lesions (45 malignancies and 59 nonmalignancies) was detected under white light and narrow band imaging modes. The sensitivity and specificity of narrow band imaging in detecting malignant lesions were 88.9 and 93.2 per cent, respectively. The intraepithelial papillary capillary loop classification, as determined by narrow band imaging, was closely associated with the laryngeal lesions' histological findings. Type I to IV lesions were considered nonmalignant and type V lesions malignant. For type Va lesions, the sensitivity and specificity of narrow band imaging in detecting severe dysplasia or carcinoma in situ were 100 and 79.5 per cent, respectively. In patients with type Vb and Vc lesions, the sensitivity and specificity of narrow band imaging in detecting invasive carcinoma were 83.8 and 100 per cent, respectively., Conclusion: Narrow band imaging is a promising approach enabling in vivo differentiation of nonmalignant from malignant laryngeal lesions by evaluating the morphology of mucosal capillaries. These results suggest endoscopic narrow band imaging may be useful in the early detection of laryngeal cancer and precancerous lesions.

Objective: To evaluate the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in cases of undiagnosed intrapulmonary lesions., Methods: A total of 89 patients with intrathoracic lesions underwent EBUS-TBNA, including 56 pulmonary lesions, 7 lymph node staging in lung cancer patients, 21 unknown hilar and/or mediastinal lymphadenopathies and 5 mediastinal tumors. All samples were evaluated for cytological and pathological examinations., Results: No complication of EBUS-TBNA was observed. Among 89 cases, 76 had positive results, 5 negative and 5 cases excluded as unsatisfied samples. In 56 patients with pulmonary lesions, EBUS-TBNA demonstrated 45 malignant tumors, 5 benign diseases, 3 suspicious cancers, 1 negative and 2 unsatisfied samples. In 7 lung cancer patients staged by EBUS-TBNA, 5 showed metastasis and 2 showed no metastasis. In 21 cases with mediastinal and/or hilar lymphadenopathy, EBUS-TBNA demonstrated 3 malignant tumors, 13 benign diseases, 2 negative and 3 unsatisfied samples. All 5 mediastinal lesions were malignant. Three suspicious cancers were confirmed, 1 by CT-guided percutaneous transthoracic needle biopsy and 2 by clinical follow-ups. In 2 lung cancer patients EBUS-TBNA showed negative, 1 surgical sample showed metastasis and another no metastasis by PET-CT. Three negative cases were diagnosed as benign by clinical follow-ups. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were 95%, 100%, 100% and 20% respectively., Conclusion: EBUS-TBNA is both effective and safe in making a diagnosis of intrathoracic lesions.

Objective: To investigate the value of narrow band imaging (NBI) endoscopy in the detection of laryngeal cancer and its precursor lesions., Methods: Between December 2008 and July 2009, a total of 122 consecutive patients with suspected precancerous or cancerous lesions of the larynx were enrolled in this study. High performance endoscopic system equipped with the white light mode and NBI mode was introduced in the examination of larynx. Full pharyngeal and laryngeal examination was performed first under white light endoscope and then under NBI. Each lesion was observed by NBI endoscopy and classified according to the detailed morphologic findings of epithelial microvessels. Histological results were then compared to the corresponding white light and NBI images., Results: Among the 122 patients, a total of 149 lesions were detected by white light and NBI modes. The histological diagnoses of these lesions were as follows: 16 laryngeal polyp, 7 laryngitis, 24 simple hyperplasia, 17 mild dysplasia, 6 moderate dysplasia, 6 severe dysplasia, 9 carcinoma in situ, 64 invasive cancer. The diagnostic accuracy by NBI for the laryngeal lesions was 90.6% (135/149), which was significantly higher than that of white light (75.2%, 112/149, chi² = 12.514, P < 0.001). The sensitivity of NBI and white light to detect laryngeal carcinoma was 93.2% (68/73) and 68.5% (50/73), respectively (chi² = 14.317, P < 0.001)., Conclusions: NBI endoscopy was a promising tool for the differentiation of non-malignant from malignant laryngeal lesions in vivo by detection of the morphology of mucosal capillary vessels. NBI endoscopy was easy to application in the routine pharyngolaryngeal examination with high sensitivity, and facilitated to improve the abilities of preoperative diagnosis and postoperative surveillance.

High temperature coal tar was used as raw materials, and was distilled to 280 degrees C for getting coal tar soft pitch. Then refined soft pitch was obtained by solvent extracting and subsequent settlement method. Its soft point was 32 degrees C; the group compositions consisted of 53.67% heptane soluble, 39.47% heptane insoluble but toluene soluble, 6.86% toluene insoluble and 0.06% quinoline insoluble. The relative average molecular weight was about 292. Its average molecular formula was C22.22 H16.32 N0.12 S0.06 O0.33; the total content of heteroatom was less than 1. IR analytic results showed that its heteroatom O existed in the R-O-R and Ar-O-R structure; its heteroatom N existed in the R-NH-R and -N=, with the latter being primary. Its average structure was obtained by improved Brown-Lander model: five-membered condensed rings. UV analysis indicated that the majority was linear arrangement, and the minority was surface arrangement; namely, the chemical structure of the samples was mainly the cata-condensed structure, while the minority was peri-condensation.

Objective: To evaluate the value of transbronchial needle aspiration (TBNA) combined with transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of mediastinal and pulmonary hilar lesions as well as in the lymph node staging (N staging) of lung cancer., Methods: 129 patients with mediastinal and pulmonary hilar lesions underwent either TBNA or EUS-FNA with cytological needle aspiration. The samples obtained from TBNA or EUS-FNA were examined by both cytologiy and histopathology., Results: Of the 129 patients, 59 underwent TBNA and 70 EUS-FNA. The diagnostic rate were 84.7% (50/59) by TBNA and 94.3% (66/70) by EUS-FNA, resepectively. The diagnosis of 116 (89.9%) patients were confirmed by either TBNA or EUS-FNA. The pathological and cytological diagnostic rates were 92.2% (107/116) and 88.0% (102/116), resepectively. The diagnostic rate was elevated by 8.4% (9/107) through pathological examination. The histological classification rates by cytological and pathological examination were 73.8% (76/116) and 89.3% (92/103), respectively. The diagnostic rate of histological classification was elevated by 35.5% (27/76) through pathological examination., Conclusion: The combination of TBNA and EUS-FNA can improve the diagnostic rate for wider mediastinal and pulmlonary hilar lesions. Pathological examination of the samples obtained from the TBNA and EUS-FNA can elevate not only the rate of diagnosis but also the rate of histological classification.

Objective: To study the rule of development of early cancer of gastric cardia in vivo in public screening., Methods: A prospective cohort study on gastric cardiac cancer was held in the high incidence area of cancer of esophagus and stomach in China. 106 subjects had been examined regularly by endoscopy to observe the change of mucosa in high incidence area of gastric cardiac carcinoma developing at the root of gastric cardiac ridge by taking serial biopsy specimens. All specimens were diagnosed through the normal pathological processes to study the prognosis of pre-cancerous lesion of gastric cardia., Results: The result of 106 subjects who had been observed for four years were: 1. Of 8 normal persons, 3 stayed normal, 4 turned to chronic gastritis, 1 developed early gastric cardiac cancer. 2. Of 61 persons chronic gastritis, 11 was observed to have glandular atrophy, 4 with mild atypical hyperplasia, and 2 with highly atypical hyperplasia. 3. Of 9 subjects showing atrophic chronic gastritis, 5 revealed no change, and 4 became chronic gastritis. 4. Of 22 subjects who revealed mild atypical hyperplasia, 17 resolved, 4 showed no change, and 1 advanced to highly atypical hyperplasia. 5. One person with highly atypical hyperplasia reverted to mild atypical hyperplasia. 6. Of 5 subjects with early gastric cardiac cancer without any treatment, 1 became advanced cancer, 1 still stayed in early stage, and 3 turned to atypical hyperplasia., Conclusion: 1. The development of early cancer of gastric cardia would proceed through the stages of chronic gastritis, glandular atrophy, and atypical hyperplasia. 2. The early cancer and pre-cancerous lesion of gastric cardia is reversible, though possessing malignant possibility.

Objective: The aim of this study is to evaluate the relationship between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis., Methods: A balloon cytological screening was conducted in 4000 participants in high-risk area of esophageal cancer in 1997-1998, 1050 out of these 4000 participants were confirmed as abnormal by cytology. Among them, 867 were given endoscopy examination during which mucosal stain with 1.2% iodine solution was used. The stain images were graded as four categories: Grade 1, dark yellow, protruding inlay-like with clear borders and showing pink after discoloration; Grade 2, between grade 1 and grade 3; Grade 3, light yellow, flat lesion with clear but not sharp borders and Grade 4, dark-brown color. According to the above criteria, the lesions were recorded and graded after the examination. The biopsies were taken from the unstained lesions and underwent pathologic evaluation. A comparison between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis was evaluated. The correlation coefficient was estimated using Spearman's Rank Correlation., Results: 94.4% (68/72) of the superficial carcinoma and severe dysplasia, 61.8% (73/118) of moderate dysplasia and 27.7% (35/126) of mild dysplasia were distributed in the grade 1 and grade 2 of iodine stain images of which the patterns conforming to the principle and rule of formation of the image by iodine stain., Conclusion: There is close relationship between the imaging patterns of endoscopy aided by iodine stain and histological diagnosis. The magnitude of exposure of the malignant tissue is the pathologic basis of formation of various images by iodine stain. Iodine stain greatly helps of early detection of esophageal cancer.

Objective: To explore the effect of endoscopic esophageal mucosal resection using transparent cap-fitted endoscope to treat early esophageal cancer and severe hyperplasia, precancerous lesion of esophageal cancer., Methods: Endoscopic esophageal mucosal resection were performed with transparent-cap technique on 29 cases of early esophageal cancer and 42 cases of severe hyperplasia, and the residual lesions were treated by Argon plasma coagulation (APC). All patients were followed up by endoscopic examination one month, 4 months, and 12 months after the therapy., Results: (1) Local esophageal mucosa with the size of 21.8 mm +/- 1.02 mm x 18.2 mm +/- 1.02 mm on average was resected from 71 cases, with 88 lesions, using transparent cap-fitted endoscope. 1:1,000 saline-epinephrine at an average dose of 18 ml was injected submucosally for each lesion. (2) After the mucosectomy 5 cases had bleeding which was controlled successfully by compression, local injection of saline-epinephrine, and APC. None case suffered from perforation. Stenosis was found in 4 cases after mucosal resection, in three of which the extent of resected mucosa exceeded 3/4 of the esophageal circumference. Water-balloon dilator was used once a month for 3 - 4 times since one month after mucosal resection. All cases were cured. (3) The lesions of 58 cases (81.2%) were completely resected, and the remaining cases had residual lesions that were treated by APC. Three cases of early cancer and 2 cases of severe atypical hyperplasia were discovered endoscopically 4 months after resection and were cured by APC. (4) All cases survived without any discomfort after a follow-up of 4.6 months on average., Conclusion: Safe, simple, minimally invasive and effective on early esophageal cancer and precancerous lesion, endoscopic esophageal mucosal resection (EEMR) is promising clinically.

Screening of hollow-organ cancers has been carried out for 16 years using the occult blood test. We are currently assessing the result of serial public cancer screening in China. Human cancers can be divided into 3 types: 1) surface cancer (15%), 2) hollow-organ cancer (65%), and 3) deep-seated solid-organ cancer (20%). Through an education program, the general population was taught to self-examine the body surface and to use a self-examination kit to detect any occult blood discharged from the hollow organs. On discovering positive or doubtful results, these subjects were referred to the hospital for a complete clinical checkup. A total of 10,000 people ages 40 to 70 years chosen from the university areas in Beijing were divided in a test group (5,000) and a control group (5,000). This study, which was carried out for 4 years, showed that 79 cancers were discovered in the test group, with an annual cancer detection rate of 482.5/10,000 population and a cancer mortality rate of 36.6/10,000. The control group showed an annual cancer mortality rate of 206/10,000 population. The difference has very marked statistical significance ( p< 0.001). During the same interval, an extensive cancer screening was carried out in the high-incidence areas. The Cancer Institute in Sihui city of Guangdong province discovered, by screening 758 persons in the outpatient department during a 2-year period, 16 cancers with 15 as nasopharyngeal cancer. From 1999 to 2000, another extensive public cancer screening in the high-incidence areas in Jiangsu province discovered 480 cancers from an 80,000 population. Together with the screening test carried out by Qin's self-examination kit before the National Supported Cancer Research Project on a population of 431,000, 1,272 cancers and more than 10,000 precancerous lesions have been detected. The self-examination kit and public cancer screening are highly important in the practice of public cancer screening.