[Effects of stress-induced protein Sestrin2 on necroptosis of dendritic cells induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of stress-induced protein Sestrin2 (SESN2) on necroptosis of mouse dendritic cell (DC) induced by lipopolysaccharide (LPS) combined with zVAD, a panaspartate-specific cysteine protease (caspase) inhibitor. METHODS: The DC2.4 cell line derived from the bone marrow of mouse in the 3rd to 10th generations was cultured. The cells were stimulated with LPS for 0 hour, 6 hours, 12 hours, and 24 hours, and grouped according to the stimulation time points. Western blotting was performed to determine the protein expression of SESN2 in each group. Overexpression empty lentivirus (NC), SESN2 gene overexpression RNA sequence lentivirus (SESN2 LV-RNA), small interfering empty lentivirus (NS), and SESN2 gene small interfering RNA sequence lentivirus (SESN2 siRNA) were transfected into DC2.4 cells. After 72 hours of transfection, cell fluorescence expression was observed under the inverted fluorescence microscope. Cells in each transfection group were stimulated with LPS for 24 hours. The blank control groups were set up and cultured with phosphate buffered saline (PBS) for 24 hours. Western blotting was performed to measure SESN2 protein expression. In the same groups as above, cells were stimulated with LPS+zVAD for 24 hours. The blank control groups were set up and cultured with PBS for 24 hours. Western blotting was used to determine the expression of mixed lineage kinase domain-like protein (MLKL) and phosphorylated-MLKL (p-MLKL). The p-MLKL levels and the number of positive cells were observed using laser scanning confocal microscopy. The necroptotic cell ratios were assessed by both flow cytometry and Hoechst staining. RESULTS: Compared to the LPS 0 hour group, the expression of SESN2 in the LPS 24 hours group showed a significant increase. Therefore, 24 hours was chosen as the subsequent stimulation time point. After successful lentivirus transduction and 24 hours of cultivation, the MLKL phosphorylation level in the SESN2 siRNA+LPS+zVAD group was significantly higher than that in the NS+LPS+zVAD group. The MLKL phosphorylation in the SESN2 LV-RNA+LPS+zVAD group was significantly lower than that in the NC+LPS+zVAD group. The MLKL phosphorylation levels in both the NS+LPS+zVAD group and the NC+LPS+zVAD group were obviously higher than those in the NS+PBS group and the NC+PBS group, respectively. Laser scanning confocal microscopy showed that the trends in quantity and fluorescence intensity of p-MLKL protein expressions were consistent with the above results. The results from flow cytometry analysis and Hoechst staining showed that the rates of cell necrotic apoptosis in SESN2 siRNA+LPS+zVAD group were significantly higher than those in NS+LPS+zVAD group [flow cytometry analysis: (30.800±1.153)% vs. (20.800±1.114)%, Hoechst staining: (75.267±0.451)% vs. (46.267±3.371)%, both P < 0.05], indicating that knocking down SESN2 further exacerbated the occurrence of necroptosis. The necrotic apoptosis rates in SESN2 LV-RNA+LPS+zVAD group were significantly lower than those in NC+LPS+zVAD group [flow cytometry analysis: (7.160±0.669)% vs. (19.240±2.322)%, Hoechst staining: (32.433±3.113)% vs. (48.567±4.128)%, both P < 0.05], indicating that overexpressing SESN2 reversed such response and markedly reduced the proportion of necroptotic cells compared to the corresponding empty vector group. CONCLUSIONS: SESN2 exhibits an inhibitory effect on necroptosis of DC in sepsis. Targeted SESN2 expression may regulate the process of DC-mediated immune response in sepsis.

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.

Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.

Interleukin (IL)- 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.

Effect of Wet-Dry Cycling on Properties of Natural-Cellulose-Fiber-Reinforced Geopolymers: A Short Review.

To study the long-term properties of cement-based and geopolymer materials exposed to outdoor environments, wet-dry cycles are usually used to accelerate their aging. The wet-dry cycling can simulate the effects of environmental factors on the long-term properties of the composites under natural conditions. Nowadays, the long-term properties of geopolymer materials are studied increasingly deeply. Unlike cement-based materials, geopolymers have better long-term properties due to their high early strength, fast hardening rate, and wide range of raw material sources. At the same time, natural cellulose fibers (NCFs) have the characteristics of abundant raw materials, low price, low carbon, and environmental protection. The use of NCFs as reinforcements of geopolymer matrix materials meets the requirements of sustainable development. In this paper, the types and properties of NCFs commonly used for geopolymer reinforcement and the polymerization mechanism of geopolymer matrix materials are summarized. By analyzing the properties of natural-cellulose-fiber-reinforced geopolymers (NCFRGs) under non-wet-dry cycles and NCFRGs under wet-dry cycles, the factors affecting the long-term properties of NCFRGs under wet-dry cycles are identified. Meanwhile, the degradation mechanism and mechanical properties of NCFRG composites after wet-dry cycles are analyzed. In addition, the relationship between the properties of composites and the change of microstructure of fiber degradation is further analyzed according to the results of microscopic analysis. Finally, the effects of wet-dry cycles on the properties of fibers and geopolymers are obtained.

The role of IL-6, IL-10, TNF-α and PD-1 expression on CD4 T cells in atrial fibrillation.

Backgrounds: While not completely understood, the electrical, structural, and communication pathways that play a role in the onset and progression of atrial fibrillation (AF) seem to be connected to the intricate interplay between neurohormones and cellular mediators. Our study's objective was to examine how the expression profiles of the inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and programmed death 1 (PD-1) changed in Cluster of Differentiation 4 (CD4) T cells depending on whether atrial fibrillation was paroxysmal or permanent. This analysis would provide new diagnostic markers for the detection and management of atrial fibrillation. Methods: In a cross-sectional study, 60 healthy controls, 49 patients with persistent atrial fibrillation, and 50 patients with paroxysmal atrial fibrillation were compared. Serum biomarker levels are found using the ELISA method, which uses enzyme-linked immunosorbent assay. Echocardiography was used to assess heart function. Results: Patients with atrial fibrillation had serum concentrations of IL-6, TNF-a, and IL-10 that were considerably higher than but PD-1 was lower those in the non-AF control group and those in patients with persistent atrial fibrillation. According to the diameter of LA and the serum level of NT-proB-type natriuretic peptide (NT-proBNP) is greater than that of patients with paroxysmal atrial fibrillation than control group. Patients with persistent atrial fibrillation had increased serum levels of low-density lipoprotein cholesterol (LDL-C) compared with those without atrial fibrillation. While PD-1 in patients with paroxysmal atrial fibrillation is closely related to C-reactive protein (CRP), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and very low density lipoprotein cholesterol. In addition, PD-1 in patients with persistent atrial fibrillation is closely related to IL-6, TNF-a, and IL-10. Conclusion: Higher blood concentrations of NT-proBNP, IL-6, IL-10, TNF-, and LDL-C but low level of PD-1 are associated with progression from paroxysmal or chronic AF.

The Effect and Mechanism of POSTN and Its Alternative Splicing on the Apoptosis of Myocardial Cells in Acute Myocardial Infarction: A Study in Vitro.

Our study aimed to investigate key molecular targets in the pathogenesis of AMI, and provide new strategy for the treatment. In this work, the myocardial ischemia and hypoxia model was constructed by using HL-1 mouse cardiomyocytes. The over-expressing POSTN wild-type, mutant and negative control lentiviruses (GV492-POSTNWT,GV492-POSTN-MUT, GV492-NC) was conducted and transfected. Cardiomyocytes were examined for cell proliferation and apoptosis to explore the effects of POSTN and its alternative splicing. The endoplasmic reticulum stess-related apoptosis proteins were selected and detected. We found that POSTN could promote the proliferation of normal and hypoxic cardiomyocytes and inhibit their apoptosis. The mechanism by which POSTN inhibited cardiomyocyte apoptosis may be through inhibiting the GRP78-eIF2α-ATF4-CHOP pathway of endoplasmic reticulum stress. Alternative splicing of POSTN could inhibit the apoptosis of ischemic and hypoxic cardiomyocytes, and its mechanism needs to be confirmed by further studies. We drawed the conclusion that POSTN might be a potential therapeutic target for AMI.

Candidate genes and their alternative splicing may be potential biomarkers of acute myocardial infarction: a study of mouse model.

BACKGROUND: Acute myocardial infarction (AMI) is one of the leading causes of death in human being, and an effective diagnostic biomarker is still lacking. Whilst some gene association with AMI has been identified by RNA sequencing (RNA-seq), the relationship between alternative splicing and AMI is not clear. METHODS: We retrieved myocardial tissues within 24 h from mice with induced AMI and sham, and analysed the differentially expressed genes (DEGs) and differential alternative splicing genes (DASGs) by RNA-seq. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein interaction network analysis were performed on DEGs-DASGs-overlap genes. PCR was used to verify the expression levels of representative genes and alternative splicing in myocardial tissues of AMI and sham mice. RESULTS: 1367 DEGs were identified, including 242 up-regulated and 1125 down-regulated genes, among which there were 42 DASGs. GO analysis showed that the cellular component was primarily enriched in plasma membrane, cell membrane integrity and extracellular region. The molecular function was enriched in protein binding and metal ion binding. The biological process was primarily enriched in cell adhesion, immune system process and cell differentiation. KEGG analysis showed the enrichment was mainly in JAK-STAT and PI3K-AKT signalling pathway. Postn, Fhl1, and Fn1 were low-expressed while Postn alternative splicing was high-expressed in myocardial tissue of AMI mice, which was consistent with sequencing results. CONCLUSIONS: The pathogenesis of AMI involves differentially expressed genes and differential alternative splicing. These differentially expressed genes and their alternative splicing, especially, Fhl1, Fn1 and Postn may become new biomarkers of AMI.

Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma.

BACKGROUND: Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood. METHODS: Public databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs. RESULTS: Initially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRT-PCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis. CONCLUSION: TRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma.

Predictors of Stent Restenosis in Han and Uygur Patients with Coronary Heart Disease after PCI in the Xinjiang Region.

Background: Stent restenosis after PCI seriously affects the efficacy and prognosis; therefore, the study of ISR risk factors has become an urgent topic to be solved. Objective: To investigate the risk factors for in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) in Han and Uygur patients with coronary heart disease. Methods: The clinical data of 345 Han and 127 Uygur patients who underwent intracoronary stent implantation were divided into an ISR group and a non-ISR group. The general clinical data, laboratory indicators, and coronary artery lesions were compared. Results: Age (OR = 1.040, 95% CI: 1.006∼1.075), triglycerides (OR = 1.440, 95% CI: 1.050∼1.973), total cholesterol (OR = 5.256, 95% CI: 2.826∼9.773), and ApoB (OR = 137.540, 95% CI: 11.364∼899.455) were independent risk factors for ISR after PCI in the Han patients, while ApoAI (OR = 0.002, 95% CI: 0.001∼0.011), MCV (OR = 0.824, 95% CI: 0.744∼0.911), MCH (OR = 0.421, 95% CI: 0.324∼0.548), and MCHC (OR = 0.934, 95% CI: 0.903∼0.965) were protective factors of ISR after PCI in Han patients, and the logistic regression equation composed of various factors predicted that the area under the ROC curve of ISR was 0.905. ApoB (OR = 11.571, 95% CI: 1.667∼80.340), Gensini score (OR = 1.017, 95% CI: 1.003∼1.031), and diabetes history (OR = 3.474, 95% CI: 1.189∼10.151) were independent risk factors for ISR after PCI in Uygur patients, and the area under ROC curve of ISR predicted by logistic regression equation is 0.807. The predictive efficiency of the Gensini score and ApoB level for ISR in Uygur patients was higher than that in Han, while the predictive efficiency of levels of ApoAI and MCH for ISR in Han patients was higher than that in Uygur (P < 0.05). Conclusion: The independent risk factors for ISR after PCI in Han and Uygur patients in Xinjiang are different.

Pyroptosis in sepsis: Comprehensive analysis of research hotspots and core genes in 2022.

Sepsis, a life-threatening disease caused by dysregulated host response to infection, is a major public health problem with a high mortality and morbidity rate. Pyroptosis is a new type of programmed cell death discovered in recent years, which has been proved to play an important role in sepsis. Nevertheless, there is no comprehensive report, which can help researchers get a quick overview and find research hotspots. Thus, we aimed to identify the study status and knowledge structures of pyroptosis in sepsis and summarize the key mechanism of pyroptosis in sepsis. The data were retrieved and downloaded from the WOS database. Software such as VOSviewer was used to analyze these publications. Key genes were picked out by using (https://www.genecards.org) and (http://www.bioinformatics.com). Then, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to performed these key genes. From 2011 to 2021, a total of 299 papers met the search criteria, and the global interest in pyroptosis in sepsis measured by the value of (RRI) has started to increase since 2016. China ranked first in the number of publications, followed by the USA. The journal Frontiers in Immunology published the most relevant articles. Through keyword co-occurrence analysis, the high-frequency subject terms were divided into three clusters like "animal research", "cell research," and "molecular research" clusters. "mir," "aki," "monocyte," and "neutrophil" were the newest keywords that may be the hotspot. In addition, a total of 15 genes were identified as hub genes. TNF, IL-1ß, AKT1, CASP1, and STAT3 were highly expressed in lung tissues, thymus tissues, and lymphocytes. KEGG analysis indicated that pyroptosis may play a vital role in sepsis via the NOD, PI3K/AKT, and MAPK/JNK pathways. Through the quantitative analysis of the literature on pyroptosis in sepsis, we revealed the current status and hotspots of research in this field and provided some guidance for further studies.

Analysis of risk factors for different subtypes of acute coronary syndrome.

AIMS: To investigate the different risk factors among different subtypes of patients with acute coronary syndrome (ACS). METHODS: A total of 296 patients who had ACS were retrospectively enrolled. Blood and echocardiographic indices were assessed within 24 hours after admission. Differences in risk factors and Gensini scores of coronary lesions among three groups were analyzed. RESULTS: Univariate analysis of risk factors for ACS subtypes showed that age, and levels of fasting plasma glucose, amino-terminal pro-brain natriuretic peptide, and creatine kinase isoenzyme were significantly higher in patients with non-ST-segment elevation myocardial infarction (NSTEMI) than in those with unstable angina pectoris (UAP). Logistic multivariate regression analysis showed that amino-terminal pro-brain natriuretic peptide and the left ventricular ejection fraction (LVEF) were related to ACS subtypes. The left ventricular end-diastolic diameter was an independent risk factor for UAP and ST-segment elevation myocardial infarction (STEMI) subtypes. The severity of coronary stenosis was significantly higher in NSTEMI and STEMI than in UAP. Gensini scores in the STEMI group were positively correlated with D-dimer levels (r = 0.429) and negatively correlated with the LVEF (r = -0.602). CONCLUSION: Different subtypes of ACS have different risk factors. Our findings may have important guiding significance for ACS subtype risk assessment and clinical treatment.

Relationship between M235T and T174M polymorphisms in angiotensin gene and atrial fibrillation in Uyghur and Han populations of Xinjiang, China.

OBJECTIVE: To elucidate the association between angiotensin gene (AGT) M235T and T174M genetic polymorphisms in Han and Uyghur patients with atrial fibrillation (AF) in Xinjiang, China. METHODS: 100 cases of patients with AF of Han and 100 cases of patients with AF of Uyghur were selected as the experimental group, and 100 cases of patients with non-AF of Uyghur and non-AF of Han were selected as the control group. We amplified the AGT M235T site and AGT T174M site by PCR in 4 groups of patients, verified the polymorphism of the sites by gene sequencing, and compared their differences in each group. RESULTS: The high risk factors for AF such as sex, left atrial diameter (LAD), right atrial diameter (RAD), and coronary heart disease were significantly different between the Han case group and the control group (P < 0.05). There were significant differences in age, LAD, RAD, coronary heart disease and smoking as contributors to AF between Uyghur case group and control group (P < 0.05). The genotype frequency distribution of AGT M235T and AGT T174M loci in the AF group and control group of Han and Uyghur was in accordance with Hardy-Weinberg equilibrium law test. There was a significant difference in genotype frequency and allele frequency of AGT M235T locus between Han group, Uyghur AF group and control group (P < 0.05). CONCLUSION: The AGT M235T and AGT T174M loci were associated with the occurrence of atrial fibrillation in the Han and Uyghur ethnic groups in Xinjiang.

Correlation between P-selectin rs1800807 and rs1800808 Gene polymorphisms and plasma soluble P-selectin concentrations in patients with atrial fibrillation complicated with thromboembolism in Xinjiang, China.

This study is to investigate the relationship of P-selectin (Ps) gene rs1800807 and rs1800808 polymorphisms with plasma soluble P-selectin (sPs) in Han, Uygur, and Kazakh people with atrial fibrillation (AF) and thromboembolism (TE) in Xinjiang, China.A total of 778 Han patients (including 131 patients with AF and TE, 229 patients with AF and 418 healthy individuals), 660 Uygur patients (including 118 patients with AF and TE, 232 patients with AF and 310 healthy individuals), and 505 Kazakh patients (including 42 patients with AF and TE, 156 patients with AF and 307 healthy individuals) were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis were used to analyze the polymorphisms of rs1800807 and rs1800808 of Ps gene. ELISA was used to determine the plasma sPs level. The association between plasma sPs levels and Ps gene polymorphisms was further analyzed.The sPs concentrations of GG genotype at rs1800807 locus in the Han, Uygur and Kazakh ethnic groups in Xinjiang, China were significantly higher than those of the CC genotype and CG genotype (P < .05). In the rs1800808 locus, plasma sPs concentrations of the heterozygous mutant CT genotypes in Han and Uygur populations were significantly higher than those in the CC and TT genotypes, whereas the plasma sPs concentrations in Kazakh TT genotypes were significantly higher than those in the CC and CT genotypes (P < .05). Among different ethnic groups, there were significant differences in sPs levels of rs1800807 and rs1800808 genotypes (P < .05).Plasma sPs concentrations are associated with Ps genotypes and sPs concentration of the same genotype shows racial differences.

Prognostic value of glucose metabolism for non-ST-segment elevation infarction patients with diabetes mellitus and single concomitant chronic total occlusion following primary percutaneous coronary intervention.

Glucose metabolism status may play a predictive role in the severity of the complications among patients with type 2 diabetes mellitus (DM). However, few studies have focused on the prognostic value of glycosylated hemoglobin (HbA1c) and Homeostatic Model Assessment 2 for Insulin Resistance (HOMA2-IR) in patients with DM, non-ST-segment elevation infarction (NSTEMI), and single concomitant chronic total occlusion (CTO) following primary percutaneous coronary intervention (PCI). Short- and long-term prognostic value of HbA1c and HOMA2-IR in patients with DM with NSTEMI and single CTO who received primary percutaneous transluminal coronary intervention (pPCI).Data from 202 patients with NSTEMI and single CTO in nonculprit vessels were included. The incidence of revascularization, cardiogenic shock, ischemic stroke, major bleeding (ie, cerebral hemorrhage or massive hemorrhage of gastrointestinal tract), and cardiac death were combined as composite end points (CEPs). HbA1c was measured on admission and at 12 and 24 weeks after discharge. HOMA2-IR was measured on admission and at 6 and 12 weeks after discharge. The mean value of HbA1c and HOMA2-IR was calculated to determine the impact on 2.5-year CEPs. All patients were assessed during hospitalization and followed for up to 2.5 years after discharge.Mean age was 62.4 ±â€Š11.8 years and 76% were male. Previous MI, lower left ventricular ejection fraction, and higher HbA1c (hazard ratio [HR] = 1.216; 95% confidence interval [CI] = 1.023-1.445; P = .023) were independently associated with a poor prognosis at 2.5 years. Higher HbA1c and HOMA2-IR on admission was associated with CEPs during hospitalization. Mean HOMA2-IR prior to pPCI was associated with revascularization (HR = 1.129; 95% CI = 1.008-1.265; P = .036) and ischemic stroke (HR = 1.276; 95% CI = 1.044-1.560; P = .017) during the 2.5 years follow-up period.Glucose metabolism status reflected by HbA1c and HOMA2-IR may provide prognostic value to patients with NSTEMI, type 2 DM, and single concomitant CTO following PCI. Therefore, patients with NSTEMI, CTO, and poor glycemic control should be carefully evaluated prior to PCI.

Association between aldosterone synthase (CYP11B2) -344C/T polymorphism and atrial fibrillation among Han and Kazak residents of the Xinjiang region.

OBJECTIVES: Atrial fibrillation (AF) is one the most common and complex types of clinical arrhythmia syndromes. In recent years, an association between CYP11B2 gene polymorphisms and atrial myocardial fibrosis has received a significant amount of attention. This study explores the relationship between CYP11B2 gene-344C/T polymorphism and AF among Kazak and Han residents in the Xinjiang region and further clarifies the molecular mechanisms of atrial fibrillation. METHODS: The study is a case-control study using traditional methods. We selected 156 Kazak and 203 Han patient cases in the Xinjiang region who had non-valvular atrial fibrillation as well as 307 Kazak and 418 Han cases of non-AF patients as a control group. Blood samples were collected, and DNA was extracted from the peripheral blood samples. The presence of the CYP11B2 gene-344C/T polymorphism was determined using polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP). Differences in the genotypes and allele distributions among the 2 groups were compared using Statistical Package for Social Science (SPSS) 17.0 statistical software. Student's t test, the chi-squared test and logistic regression methods were used for the data analysis. RESULTS: The genotypes of both ethnic groups followed a Hardy-Weinberg genetic equilibrium distribution. The 2 patient groups, compared with their respective control groups, showed significant dominant models in CYP11B2 gene-344C/T polymorphism genotype frequency and B1 allele frequency (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphism in the Kazak patient group were higher compared with the control groups (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphisms in the Han patient group was also higher compared with the control group (P<0.05). Logistic regression analysis showed that the frequencies of the CYP11B2 gene-344C/T genotypes were significantly different between the Kazak and Han patient groups and the control groups. CONCLUSION: CYP11B2 gene -344C/T polymorphism is associated with AF.

Analysis of the risk factors and characteristics of coronary artery disease of Han, Uygur and Kazak patients with acute myocardial infarction in Xinjiang district.

To discuss the risk factors and characteristics of coronary artery disease of Han, Uygur and Kazak patients with acute myocardial infarction in Xinjiang district. A retrospective analysis of clinical data of 262 cases of Han patients, 166 cases of Uygur patients and 86 cases of Kazak patients was conducted, whose age, body mass index, cholesterol, uric acid, hypertension, type 2 diabetes, smoking, drinking, family history of coronary heart disease, relationship between PCI history and pathogenesis of acute myocardial infarction, and coronary artery disease characteristics were observed and compared in different groups. Between the Han and minority young patients, there were statistically significant differences in the distribution of BMI, lipoprotein a, positive family history of coronary heart disease, uric acid level, the combined aspects of smoking history (P<0.017); there were also statistically significant differences in BMI, TG, HDL-C, apolipoprotein B, positive family history of coronary heart disease distribution between minority young patients and older patients (P<0.017). There were statistically significant differences in the distribution of BMI, TC, HDL-C, LDL-C, apolipoprotein AI, positive family history of coronary heart disease between Han and Uygur patients (P<0.017). Han and Kazak patients had statistically significant differences in the distribution of BMI, TC, LDL-C, apolipoprotein B, lipoprotein a, type 2 diabetes and hypertension (P<0.017). Comparison of patients in Uygur and Kazak showed that there were statistically significant differences in the distribution of BMI, TC, LDL-C, apolipoprotein AI, apolipoprotein B and type 2 diabetes between the two groups (P<0.017). The proportion of zero lesions and single-vessel lesions in minority youth patients was higher than that of elderly patients (P<0.001), and the proportion of two and three lesions was less than that of elderly patients (P<0.001). Gensini score of Han patients was greater than that of Uygur patients (P<0.001) and the Kazak patients (P=0.005); The proportion of Han patients with single-vessel disease was less than that of Kazak patients (P=0.003), and the proportion of patients with double-vessel disease was greater than that of Kazak patients (P=0.007). There were ethnic differences in risk factors and the characteristics of coronary artery disease of AMI patients in Xinjiang district; there were differences between minority youth patients and elderly patients, young patients of Han.

Association of PS gene polymorphism and soluble P-selectin levels in atrial fibrillation thromboembolism population in Xinjiang.

UNLABELLED: To investigate the association between the polymorphism of P choose element (p. selectin, PS) and soluble P-selectin levels in atrial fibrillation (AF) thromboembolism in Han and Uigur population of Xinjiang. METHOD: Using ELISA method determination of plasma level of sPs. The frequency distributions of SNP sP-selectin gene promoter (-2123C/G) and SNP in exon region (Thr715Pro) were investigated by polymerase chain reaction (PCR)-restriction fragment length polymorphism and direct DNA sequence analysis among 302 Xinjiang Uigur and 340 age- and sex-matched Han people. RESULTS: Cases sPs exist significant difference serum level and the control group. The frequencies of the -2123C/G allele among the Uigur population had no significant differences from those of the Han population. Thr715Pro did not show any polymorphism in the two populations. CONCLUSIONS: The sP-selectin gene polymorphisms are associated with serum sP-selectin levels or thromboembolic events, suggesting that the patients with nonvalvular AF and thromboembolic events may have genetic susceptibility.

Effect of periodic pacemaker optimization on left atrial reverse remodeling in long-term cardiac resynchronization therapy.

PURPOSE: Few data exist about the effect of cardiac resynchronization therapy (CRT) on left atrial (LA) reverse remodeling and function, and whether echocardiographic (echo)-guide pacemaker optimization of atrioventricular and interventricular delays could beneficially affect LA reverse remodeling in long-term CRT therapy. METHODS: Effect of periodic pacemaker optimization on LA reverse remodeling induced by CRT was analyzed in 113 consecutive patients (mean age, 60 ± 11 years) and stratified according to periodic pacemaker optimization (group 1) and nonperiodic pacemaker optimization (group 2). Left atrial volumes index percent changes were assessed at every continuing 6-month follow-up visit. The primary endpoint was LA reverse remodeling. The secondary endpoint included left ventricular reverse remodeling and left ventricular ejection fraction. RESULTS: There is no significant difference of follow-up duration in subgroups (42.43 ± 18.94 months in group 1 vs 37.76 ± 20.24 months in group 2, p = 0.228). The responder's rate of subgroups showed similar after follow-up of 12 months (60.0 vs 53.2%, p = 0.483). After 24-month follow-up, the mean reduction of LAV index was similar in two groups (10.34 vs 7.53%, p = 0.257). The improvement effect of LA reverse remodeling induced by CRT was sustained during 24-month follow-up to the end of current study in periodic pacemaker optimization group. The degree of LAV index percent reduction was directly correlated to periodic pacemaker optimization at end of current analysis (17.13 vs 10.35%, p = 0.047). CONCLUSIONS: Periodic echo-guide pacemaker optimization of atrioventricular and interventricular delays plays a positive role on LA reverse remodeling in long-term CRT therapy.

Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang.

OBJECTIVE: To study the effects of γ-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region. METHODS: Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed. RESULTS: The rs2592551 polymorphism detection results were 136 cases of wild-type homozygous CC genotype (50.56%), 115 cases of heterozygous CT genotype (42.75%), 18 cases of homozygous TT genotype (6.69%). The allele frequency C was 71.93%, T was 28.07%. The stable warfarin dose average was 2.86 ± 0.61 mg/d in patients with CC genotype, 3.59 ± 0.93 mg/d in patients with CT genotype and 4.06 ± 0.88 mg/d in patients with TT genotype. The warfarin dose in different genotypes were compared, there was statistically significant difference between CC and TT, CC and CT (P <0. 05), but the TT and CT showed no significant difference (P > 0.05). CONCLUSION: In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in GGCX gene rs259251 loci required for significantly higher warfarin dose than those with CC genotype. Therefore, rs2592551 polymorphism may one of the factors affecting the warfarin dose in patients with atrial fibrillation.

TGF-ß1 signal pathway in the regulation of inflammation in patients with atrial fibrillation.

OBJECTIVE: To observe the expression changes of inflammatory markers TGF-ß1, Smad3 and IL-6 in patients with atrial fibrillation (AF), and to explore the significance of TGF-ß1 signaling pathway in the structural remodeling of AF. METHODS: The expression of TGF-ß1, Smad3 and IL-6 in 50 cases with AF and 30 normal cases were detected by RT-PCR and ELISA. RESULTS: The TGF-ß1, Smad3 and IL-6 mRNA and protein expression levels in patients with AF were significantly higher than that in the control group (P<0.05), but there was no significantly different between the paroxysmal AF group and the persistent AF group (P>0.05). The TGF-ß1mRNA expression in the ⩾ 50 years subgroup was significantly higher than that in the <50 years subgroups, and it was higher in the NYHA III subgroup than in the I/II grade subgroup. It was also higher in the left ventricular ejection fraction (LVEF) <50% subgroup than in LVEF ⩾ 50% group, and it was significantly higher in the AF time ⩾ 36 months subgroup than that in <36 months subgroup (P<0.05). The Smad3 and IL-6 expressions in the in the LVEF <50% subgroup were both high that than that in LVEF ⩾ 50% group, and higher in the AF time ⩾ 36 months subgroup than that in <36 months subgroup (P<0.05). There were a positive correlation between TGF-ß1, Smad3 and IL-6 (r=0.687, r=0.547). There were also a positive correlation between Smad3 and IL-6 mRNA (r=0.823). CONCLUSIONS: AF is associated with inflammation, and the inflammation is also involved in the fibrillation and sustain of AF. The TGF-ß1 signal pathway may be involved in the process of atrial structural remodeling in patients with AF, and iss related with the occurrence and maintenance of AF.