Association of the stress hyperglycemia ratio with coronary artery disease complexity as assessed by the SYNTAX score in patients with acute coronary syndrome.

BACKGROUND: Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. METHODS: A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. RESULTS: Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). CONCLUSIONS: There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosis via MAPK signaling inhibition.

Reperfusion is essential for ischemic myocardium but paradoxically leads to myocardial damage that worsens cardiac functions. Ferroptosis often occurs in cardiomyocytes during ischemia/reperfusion (I/R). The SGLT2 inhibitor dapagliflozin (DAPA) exerts cardioprotective effects independent of hypoglycemia. Here, we investigated the effect and potential mechanism of DAPA against myocardial ischemia/reperfusion injury (MIRI)-related ferroptosis using the MIRI rat model and hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocytes. Our results show that DAPA significantly ameliorated myocardial injury, reperfusion arrhythmia, and cardiac function, as evidenced by alleviated ST-segment elevation, ameliorated cardiac injury biomarkers including cTnT and BNP and pathological features, prevented H/R-triggered cell viability loss in vitro. In vitro and in vivo experiments showed that DAPA inhibited ferroptosis by upregulating the SLC7A11/GPX4 axis and FTH and inhibiting ACSL4. DAPA notably mitigated oxidative stress, lipid peroxidation, ferrous iron overload, and reduced ferroptosis. Subsequently, network pharmacology and bioinformatics analysis suggested that the MAPK signaling pathway was a potential target of DAPA and a common mechanism of MIRI and ferroptosis. DAPA treatment significantly reduced MAPK phosphorylation in vitro and in vivo, suggesting that DAPA might protect against MIRI by reducing ferroptosis through the MAPK signaling pathway.

The commonness in immune infiltration of rheumatoid arthritis and atherosclerosis: Screening for central targets via microarray data analysis.

Background: Although increasing evidence has reported an increased risk of atherosclerosis (AS) in rheumatoid arthritis (RA), the communal molecular mechanism of this phenomenon is still far from being fully elucidated. Hence, this article aimed to explore the pathogenesis of RA complicated with AS. Methods: Based on the strict inclusion/exclusion criteria, four gene datasets were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the communal differentially expressed genes (DEGs) and hub genes, comprehensive bioinformatics analysis, including functional annotation, co-expression analysis, expression validation, drug-gene prediction, and TF-mRNA-miRNA regulatory network construction, was conducted. Moreover, the immune infiltration of RA and AS was analyzed and compared based on the CIBERSORT algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in RA and AS respectively. Results: A total of 54 upregulated and 12 downregulated communal DEGs were screened between GSE100927 and GSE55457, and functional analysis of these genes indicated that the potential pathogenesis lies in immune terms. After the protein-protein interaction (PPI) network construction, a total of six hub genes (CCR5, CCR7, IL7R, PTPRC, CD2, and CD3D) were determined as hub genes, and the subsequent comprehensive bioinformatics analysis of the hub genes re-emphasized the importance of the immune system in RA and AS. Additionally, three overlapping infiltrating immune cells were found between RA and AS based on the CIBERSORT algorithm, including upregulated memory B cells, follicular helper T cells and γδT cells. Conclusions: Our study uncover the communal central genes and commonness in immune infiltration between RA and AS, and the analysis of six hub genes and three immune cells profile might provide new insights into potential pathogenesis therapeutic direction of RA complicated with AS.

Analysis of the potential ferroptosis mechanism and multitemporal expression change of central ferroptosis-related genes in cardiac ischemia-reperfusion injury.

Acute myocardial infraction is the most severe type of coronary artery disease and remains a substantial burden to the health care system globally. Although myocardial reperfusion is critical for ischemic cardiac tissue survival, the reperfusion itself could cause paradoxical injury. This paradoxical phenomenon is known as ischemia-reperfusion injury (IRI), and the exact molecular mechanism of IRI is still far from being elucidated and is a topic of controversy. Meanwhile, ferroptosis is a nonapoptotic form of cell death that has been reported to be associated with various cardiovascular diseases. Thus, we explored the potential ferroptosis mechanism and target in cardiac IRI via bioinformatics analysis and experiment. GSE4105 data were obtained from the GEO database and consist of a rat IRI model and control. After identifying differentially expressed ferroptosis-related genes (DEFRGs) and hub genes of cardiac IRI, we performed enrichment analysis, coexpression analysis, drug-gene interaction prediction, and mRNA-miRNA regulatory network construction. Moreover, we validated and explored the multitemporal expression of hub genes in a hypoxia/reoxygenation (H/R)-induced H9C2 cell injury model under different conditions via RT-qPCR. A total of 43 DEFRGs and 7 hub genes (tumor protein p53 [Tp53], tumor necrosis factor [Tnf], hypoxia-inducible factor 1 subunit alpha [Hif1a], interleukin 6 [Il6], heme oxygenase 1 [Hmox1], X-box binding protein 1 [Xbp1], and caspase 8 [Casp8]) were screened based on bioinformatics analysis. The functional annotation of these genes revealed apoptosis, and the related signaling pathways could have association with the pathogenesis of ferroptosis in cardiac IRI. In addition, the expression of the seven hub genes in IRI models were found higher than that of control under different H/R conditions and time points. In conclusion, the analysis of 43 DEFRGs and 7 hub genes could reveal the potential biological pathway and mechanism of ferroptosis in cardiac IRI. In addition, the multitemporal expression change of hub genes in H9C2 cells under different H/R conditions could provide clues for further ferroptosis mechanism exploring, and the seven hub genes could be potential biomarkers or therapeutic targets in cardiac IRI.

Comparing Clinical Outcomes on Oncology Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis.

Objective: To compare the clinical outcomes of cancer and non-cancer patients with severe aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI). Methods: A computer-based search in PubMed, EMbase, The Cochrane Library, CBM, CNKI, and Wanfang databases from their date of inception to October 2021, together with reference screening, was performed to identify eligible clinical trials. Two reviewers independently screened the articles, extracted data, and evaluated their quality. Review Manger 5.3 and Stata 12.0 software were used for meta-analysis. Results: The selected 11 cohort studies contained 182,645 patients, including 36,283 patients with cancer and 146,362 patients without cancer. The results of the meta-analysis showed that the 30-day mortality [OR = 0.68, 95%CI (0.63,0.74), I 2= 0, P < 0.00001] of patients with cancer in the AS group was lower than those in the non-cancer group; 1-year mortality [OR = 1.49, 95%CI(1.19,1.88), I 2= 58%, P = 0.0006] and late mortality [OR = 1.52, 95%CI(1.26,1.84), I 2= 55%, P < 0.0001] of patients with cancer in the AS group was higher than those in the non-cancer group. The results of the meta-analysis showed that the stroke [OR = 0.77, 95%CI (0.72, 0.82), I 2= 0, P < 0.00001] and the acute kidney injury [OR = 0.78, 95%CI (0.68, 0.90), I 2= 77%, P = 0.0005] of patients with cancer in the AS group was lower than those in the non-cancer group. The results of the meta-analysis showed no statistical difference in cardiovascular mortality, bleeding events, myocardial infarction, vascular complication, and device success rate. Conclusion: It is more effective and safer in patients with cancer with severe AS who were undergoing TAVI. However, compared with patients with no cancer, this is still high in terms of long-term mortality, and further study of the role of TAVI in patients with cancer with AS is necessary. Systematic Review Registration: Identifier [INPLASY CRD: 202220009].

Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis.

Background: Cardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis. Methods: Six datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)-mRNA-microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM. Results: We found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM. Conclusion: The identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

Analysis of Communal Molecular Mechanism and Potential Therapeutic Targets in Heart Failure and Type 2 Diabetes Mellitus.

BACKGROUND: Although increasing evidence has suggested an interaction between heart failure (HF) and Type 2 diabetes mellitus (T2DM), the common mechanisms of the two diseases remain unclear. Therefore, this study aimed to obtain the differentially expressed genes (DEGs) and potential biomarkers or therapeutic targets in HF and T2DM. METHODS: The communal DEGs of HF and T2DM were identified by analyzing the two microarray datasets (GSE84796 and GSE95849), and functional annotation was performed for the communal DEGs to uncover the potential molecular mechanisms of HF and T2DM. Subsequently, STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen the hub genes. Finally, co-expression and drug-gene interaction prediction analysis and mRNA-miRNA regulatory network analysis were performed for hub genes. RESULTS: A total of 233 up-regulated genes and 3 down-regulated genes were found between HF and T2DM. The functional enrichment of DEGs and genes in each four modules were mainly involved in immunity. In addition, five hub genes were identified from PPI network, including SYK, SELL, RAC2, TLR8 and ITGAX. CONCLUSION: The communal DEGs and hub genes identified in this research contribute to discover the underlying biological mechanisms and presents potential biomarkers or therapeutic targets in HF and T2DM.

Identification of Independent and Communal Differentially Expressed Genes as Well as Potential Therapeutic Targets in Ischemic Heart Failure and Non-Ischemic Heart Failure.

BACKGROUND: Heart failure (HF) is a rapidly growing public health problem, and its two main etiological types are non-ischemic heart failure (NIHF) and ischemic heart failure (IHF). However, the independent and common mechanisms of NIHF and IHF have not been fully elucidated. Here, bioinformatic analysis was used to characterize the difference and independent pathways for IHF and NIHF, and more importantly, to unearth the common potential markers and therapeutic targets in IHF and NIHF. METHODS: Two data sets with accession numbers GSE26887 and GSE84796 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the independent and communal DEGs of NIHF and IHF, a functional annotation, protein-protein interaction (PPI) network analysis, co-expression and drug-gene interaction prediction analysis, and mRNA-miRNA regulatory network analysis were performed for DEGs. RESULTS: We found 1146 independent DEGs (DEGs2) of NIHF mainly enriched in transcription-related and 2595 independent DEGs (DEGs3) of IHF mainly enriched in immune-related. Moreover, 185 communal DEGs (DEGs1) were found between NIHF and IHF, including 93 upregulated genes and 92 downregulated genes. Pathway enrichment analysis results showed that GPCR pathways and biological processes are closely related to the occurrence of HF. In addition, three hub genes were identified from PPI network, including CCL5, C5 and TLR3. CONCLUSION: The identification of DEGs and hub genes in this study contributes to a novel perception for potential functional mechanisms and biomarkers or therapeutic targets in NIHF and IHF.

Effect of PTCD-based biliary stent placement combined with 125I particle intracavitary irradiation in treating pancreatic head cancer.

PURPOSE: To explore the efficacy and safety of percutaneous transhepatic cholangial drainage (PTCD)-based biliary stent placement combined with iodine-125 (125I) particle intracavitary irradiation versus palliative internal biliary-intestinal drainage in the treatment of pancreatic head cancer-induced obstructive jaundice. METHODS: The clinical data of 110 patients with pancreatic head cancer, who were admitted to and treated in our hospital from July 2013 to July 2016 were registered. Among them, 55 patients underwent PTCD-based biliary metallic stent placement combined with 125I particle intracavitary irradiation (125I group), while the other 55 patients received palliative internal biliary-intestinal drainage (Surgery group). The jaundice index, and liver function parameters before and after treatment, duration of stent patency, tumor growth and incidence of adverse reactions were compared between the two groups of patients, and the patient overall survival (OS) time was followed up and recorded. RESULTS: The two therapies both effectively alleviated jaundice and improved liver function in patients. There were no statistically significant differences in the preoperative liver function parameters albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) between the two groups of patients, and the liver function was significantly improved at each period of time after operation, showing a statistically significant difference. At 3 months after operation, 125I group had substantially lower levels of ALT, AST, TBIL and DBIL, but a prominently higher level of ALB than Surgery group. The complications of patients mainly included pancreatitis, recurrent biliary infections and stent blockage, which were resolved after symptomatic treatments. After operation, the maximum diameter of tumors was enlarged in both groups, and the tumor size in Surgery group and 125I group was increased from 3 months after operation to 6 months after operation, with a more obvious increase in Surgery group. The total clinical benefit rate (CBR) was 61.8% (34) and 54.5% (30), and the mean survival time of patients was 13.4±4.9 months and 12.7±4.6 months in 125I group and Surgery group, respectively. Moreover, the OS in 125I group was notably superior to that in Surgery group. CONCLUSION: PTCD-based biliary metallic stent placement combined with 125I particle intracavitary irradiation can effectively relieve jaundice, improve liver function, repress tumor growth, prolong survival and produce tolerable adverse reactions in the patients with pancreatic head cancer who lose the opportunity for surgery or are intolerant to surgery.

Syntheses, structures and properties of two 2-D layered hybrid organic-inorganic materials based on different V4O12 building units.

Two new layered hybrid organic-inorganic compounds [Zn(pyim)]2V4O12 () (pyim = 2-(2-pyridyl)imidazole) and [Cu(bim)2]2V4O12(H2O)·CH3CH2OH () (bim = bis(1-imidazolyl)methane) based on polyoxovanadates (POVs) and organic ligands decorated transition metal units have been synthesized by hydrothermal and solvothermal methods respectively. Single crystal XRD, fluorescence spectrum, magnetic measurement, IR spectra, powder XRD and thermogravimetric (TG) measurements were performed to analyze the structures and properties of and . The structural analysis reveals that compound features a two-dimensional {[Zn(pyim)]2V4O12}n layered structure, constructed by sine wave-like {V4O12}n(4n-) chains, Zn(2+) ions and pyim ligands. In the layered structure of , {V4O12}(4-) circles are connected by Cu(2+) ions to form {Cu(V4O12)}n(2n-) chains, which are further linked by {Cu(bim)4}(2+) subunits to generate a hybrid layer of . The magnetic susceptibility measurement indicates strong antiferromagnetic interactions between Cu(2+) ions in .

Dichlorido[3-meth-oxy-methyl-4-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]copper(II).

In the title complex, [CuCl(2)(C(15)H(14)N(4)O)], the Cu(II) atom possesses a highly distorted square-planar geometry with N-Cu-N and Cl-Cu-Cl angles of 79.86 (8) and 98.65 (3)°, respectively, while the Cl-Cu-N angles fall into two distinct groups with values of 95.26 (6), 98.75 (6), 150.56 (6) and 152.04 (6)°. The pyridyl ring is twisted by 9.4 (2)° with respect to the triazole ring, which is oriented at approximately right angles [84.66 (8)°] with respect to the phenyl ring.

Bis(2-hy-droxy-benzoato-κO)bis-[3-(4-meth-oxy-phen-yl)-4-(4-methyl-phen-yl)-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]copper(II) dihydrate.

In the title complex, [Cu(C(7)H(5)O(3))(2)(C(21)H(18)N(4)O)(2)]·2H(2)O, the Cu(II) atom is located on a centre of inversion and exists in a tetra-gonally distorted octahedral geometry with a CuN(4)O(2) chromophore. The intra-molecular O-H⋯O hydrogen bond is highly strained due to the mol-ecular geometry and, as a result, is much shorter than expected. Inter-molecular C-H⋯O and C-H⋯O inter-actions are also observed.

Dichloridobis[3-meth-oxy-methyl-4-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]chromium(III) chloride.

In the title complex, [CrCl(2)(C(15)H(14)N(4)O)(2)]Cl, the Cr(III) atom is located on a twofold rotation axis and is coordinated by two N,N'-bidentate triazole derivatives and two chloride ions in a distorted octa-hedral CrN(2)N'(2)Cl(2) geometry. One of the two independent Cl(-) counter-anions sits on a special position (site symmetry [Formula: see text].) and is fully occupied, whereas the other is disordered around a twofold rotation axis over two positions in a 2:3 ratio.

N'-(4-Methoxy-benzo-yl)pyridine-2-carbohydrazide.

The crystal structure of the title compound, C(14)H(13)N(3)O(3), exhibits two inter-molecular N-H⋯O hydrogen bonds.

4-(3-Methyl-phen-yl)-3-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole.

In the title compound, C(20)H(16)N(4), the m-tolyl and phenyl substituents form dihedral angles of 74.20 (6) and 36.94 (8)°, respectively, with the 1,2,4-triazole ring and the dihedral angle between the triazole and pyridine rings is 36.06 (9)°. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯π inter-actions.

Di-µ-chlorido-bis-{aqua-chlorido[3-ethyl-4-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]manganese(II)}.

In the centrosymmetric dinuclear title compound, [Mn(2)Cl(4)(C(15)H(14)N(4))(2)(H(2)O)(2)], the Mn(II) atom is coordinated by an N,N'-bidentate ligand, a water mol-ecule, a terminal chloride ion and two bridging chloride ions in a distorted MnN(2)OCl(3) octa-hedral geometry. The Mn⋯Mn separation is 3.6563 (9) Å. In the crystal structure, O-H⋯N and O-H⋯Cl hydrogen bonds help to establish the packing.

3-(2-Pyrid-yl)-5-(4-pyrid-yl)-4-(p-tol-yl)-1H-1,2,4-triazole.

In the mol-ecule of the title compound, C(19)H(15)N(5), the dihedral angles formed by the plane of the triazole ring with those of the 2-pyridyl, 4-pyridyl and p-tolyl rings are 28.12 (10), 34.62 (10) and 71.43 (9)°, respectively. The crystal structure is consolidated by C-H⋯π hydrogen-bonding inter-actions and by π-π stacking inter-actions, with a centroid-centroid distance of 3.794 (4) Å.

3-Methyl-4-(3-methyl-phen-yl)-5-(2-pyridyl)-4H-1,2,4-triazole.

In the mol-ecule of the title compound, C(15)H(14)N(4), the triazole ring is oriented at dihedral angles of 30.8 (2) and 67.4 (2)° with respect to the pyridine and benzene rings, respectively. The crystal structure is stabilized by C-H⋯N hydrogen-bonding inter-actions, forming chains of mol-ecules along [01].

Dichloridobis[3-methyl-4-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]copper(II) 3.33-hydrate.

In the title compound, [CuCl(2)(C(14)H(12)N(4))(2)]·3.33H(2)O, the Cu(II) atom is coordinated by two chelating 3-methyl-4-phenyl-5-(2-pyrid-yl)-1,2,4-triazole ligands and two chloride anions in a distorted octa-hedral geometry with a CuN(2)N(') (2)Cl(2) chromophore. The Cu atom is located on an inversion center. Two uncoordinated water mol-ecules lie on threefold rotation axes with disordered H atoms. Two hydrogen bonds are formed between the water mol-ecules, and another between water and a chlorido ligand.

Bis[3-ethyl-4-(4-methoxy-phen-yl)-5-(2-pyrid-yl)-4H-1,2,4-triazole-κN,N]bis-(perchlorato-κO)copper(II) acetonitrile disolvate.

In the title compound, [Cu(ClO(4))(2)(C(16)H(16)N(4)O)(2)]·2CH(3)CN, the Cu(II) atom, located on an inversion center, is in a tetra-gonally distorted octa-hedral environment, coordinated by four N atoms of two bidentate 3-ethyl-4-(4-methoxy-phen-yl)-5-(2-pyrid-yl)-4H-1,2,4-triazole ligands in equatorial positions and by the O atoms of two perchlorate groups in axial positions. The long axial Cu-O bond of 2.4743 (17) Šis the result of the Jahn-Teller effect.