Analysis of Risk Factors and Construction of a Predictive Model for Readmission in Patients with Coronary Slow Flow Phenomenon.

Background: Coronary slow flow phenomenon (CSFP) is a phenomenon in which distal vascular perfusion is delayed on angiography, but coronary arteries are not significantly narrowed and there is no other organic cardiac disease. Patients with CSFP may be repeatedly readmitted to the hospital because of chest pain or other symptoms of precordial discomfort, and there is a risk of adverse events. In order to investigate the risk factors affecting the readmission of CSFP patients, a prediction model was constructed with the aim of identifying patients at risk of readmission at an early stage and providing a reference for further clinical intervention. Methods: In this study, we collected clinical data from 397 CSFP patients between June 2021 and January 2023 in Xinjiang Medical University Hospital. Telephone follow-up clarified whether the patients were readmitted to the hospital. A predictive model for readmission of CSFP patients was constructed using multifactorial logistic regression. Nomogram was used to visualize the model and bootstrap was used to internally validate the model. ROC, DCA and Calibration curve were plotted to evaluate the calibration and discriminative ability of the column line graphs, respectively. Calibration and resolution of the column line graphs, respectively. Results: A total of 34 of 397 CSFP patients experienced readmission. Smoking history, creatine kinase isoenzyme-MB, total cholesterol, and left ventricular ejection fraction were the predictors of readmission in patients with CSFP. The area under the curve of the Nomogram model was 0.87, which indicated that the model had good predictive ability and differentiation, and the DCA and Calibration curves also indicated that the model had good consistency and was clinically useful. Conclusion: A readmission prediction model for patients with CSFP may facilitate early identification of patients at potential risk for readmission and timely interventional therapy to improve patient prognosis.

A case of endocardial dissection caused by Micra implantation.

BACKGROUND: Leadless pacemakers are a recent technological advancement. It has many advantages, but there are still a few serious complications. CASE PRESENTATION: This article reports the case of a patient with an endocardial tear and dissection caused by contact with the tip of the Micra cup during surgery and summarises the relevant data. CONCLUSIONS: This case report details the occurrence and management of the incident and provides some guidance for future clinical management.

Feasibility study of cryoballoon ablation for atrial fibrillation with KODEX-EPD: a single center experience.

To evaluate the feasibility of cryoballoon (CB) ablation of atrial fibrillation (AF) under the guidance of a new three-dimensional (3D) mapping system KODEX-EPD. 40 patients scheduled for CB ablation of AF in the first affiliated Hospital of Xinjiang Medical University from August 2021 to July 2022 were randomly divided into two groups: KODEX-EPD 3D mapping system guidance group (KODEX group, n = 20) and conventional two-dimensional perspective group (standard group, n = 20). The ablation time, operation time, fluoroscopy time, fluoroscopy dose, contrast agent dosage and follow-up data were compared between the two groups. Besides, the feasibility and accuracy of the dielectric sensing system in evaluating pulmonary vein (PV) occlusion in patients with AF during CB ablation were verified. All pulmonary veins were being isolated. The ablation time (36.40 ± 6.72 min vs 35.15 ± 6.29 min, P > 0.05) and the operation time (64.20 ± 11.82 min vs 66.00 ± 13.18 min, P > 0.05) were not statistically different in the two groups. The standard group has longer fluoroscopy time, dose and contrast medium dosage. There were significant differences in fluoroscopy time (532.30 ± 72.83 s vs 676.25 ± 269.33 s, P < 0.05), fluoroscopy dose (110.00 ± 28.64 mGy vs 144.68 ± 66.66 mGy, P < 0.05), and contrast medium dosage (71.90 ± 5.97 ml vs 76.05 ± 5.93 ml, P < 0.05) between the two groups. The learning curves of the first 5 patients and the last 15 patients in the KODEX group were compared. There was no statistical difference in the ablation time (36.80 ± 8.56 min vs 36.27 ± 6.34 min, P > 0.05) or the operation time (69.00 ± 5.00 min vs 62.60 ± 13.10 min, P > 0.05); however, compared to the first 5 patients, fluoroscopy time (587.40 ± 38.34 s vs 513.93 ± 73.02 s, P < 0.05), fluoroscopy dose (147.85 ± 35.19 mGy vs 97.39 ± 8.80 mGy, P < 0.05) and contrast medium dosage (79.60 ± 1.14 ml vs 69.33 ± 4.45 ml, P < 0.05) were significantly decreased. Using pulmonary venography as the gold standard, the sensitivity, specificity of the completely occlusion in KODEX group was 93.6% (95% CI 85-97.6%) and 69.6% (95% CI 54-81.8%); and the sensitivity, specificity of the small leak in KODEX group was 93.1% (95% CI 82.4-97.8%) and 82.0% (95% CI 65.9-91.9%). During an average follow-up of (9.90 ± 1.06) months, there was no statistical difference in arrhythmia recurrence and antiarrhythmic drugs taking after CB ablation between the two groups (P > 0.05). Using the KODEX-EPD system, the CB ablation procedure can correctly evaluate the PV occlusion, and significantly reduce fluoroscopy exposure and contrast medium without significantly increasing the operation time.

PON2 ameliorates Ang II-induced cardiomyocyte injury by targeting the CANX/NOX4 signaling pathway.

BACKGROUND: The incidence of heart failure (HF) presents an escalating trend annually, second only to cancer. Few literatures are available regarding on the role of paraoxonase 2 (PON2) in HF so far despite the protective role of PON2 in cardiovascular diseases. METHODS: PON2 expression in AC16 cells was examined with reverse transcriptase-quantitative polymerase chain reaction and western blot following angiotensin II (Ang II) challenging. After PON2 elevation, 2, 7-dichlorofluorescein diacetate assay estimated reactive oxygen species content, related kits appraised oxidative stress, enzyme-linked immunosorbent assay evaluated inflammatory levels, and Western blot was applied to the analysis of apoptosis levels. Research on cytoskeleton was conducted by immunofluorescence (IF), and Western blot analysis of the expressions of hypertrophy-related proteins was performed. BioGRID and GeneMania databases were used to analyze the relationship between PON2 and Calnexin (CANX), which was corroborated by co-immunoprecipitation experiment. Subsequently, PON2 and CANX were simultaneously overexpressed in AC16 cells induced by Ang II to further figure out the mechanism. RESULTS: PON2 expression was depleted in Ang II-induced AC16 cells. PON2 might mediate CANX/NOX4 signaling to inhibit oxidation, inflammatory, hypertrophy, and damage in Ang II-induced AC16 cells. CONCLUSION: PON2 can ease Ang II-induced cardiomyocyte injury via targeting CANX/NOX4 signaling.

GnRH receptor-activating autoantibodies in polycystic ovary syndrome: identification of functional epitopes and development of epitope mimetic inhibitors.

PURPOSE: We have recently demonstrated that gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). The aim of this study was to map the antigenic epitopes of GnRHR-AAb from PCOS patients, and develop retro-inverso peptide inhibitors that specifically target GnRHR-AAb. METHODS: Serum samples from ten GnRHR-AAb-positive PCOS patients and ten GnRHR-AAb-negative healthy controls were tested. Epitope mapping for GnRHR-AAb was performed using a set of 11 overlapping octapeptides spanning the second extracellular loop of GnRHR. Antibody-blocking effect of the designed retro-inverso peptide inhibitors was evaluated in a cell-based bioassay. RESULTS: Two peptide sequences, FSQCVTHC and HCSFSQWW, were found to react with all PCOS sera, but not with control sera. Two retro-inverso peptides that mimic the identified epitopes, d-CHTVCQSF and d-WWQSFSCH, significantly inhibited PCOS serum IgG-induced GnRHR activation. One of these two peptide inhibitors, d-CHTVCQSF, largely suppressed autoantibody-induced GnRHR activation, suggesting that the epitope sequence FSQCVTHC may be a major functional target of GnRHR-AAb. CONCLUSION: We have identified a dominant functional epitope for GnRHR-AAb associated with PCOS, and demonstrated effective blocking of GnRHR-AAb activity with epitope-mimicking retro-inverso peptide inhibitors. These proteolytically stable decoy peptides may have important therapeutic implications in subjects who harbor these autoantibodies.

NLRC5 enhances autophagy via inactivation of AKT/mTOR pathway and ameliorates cardiac hypertrophy.

The aim of this study was to investigate the effect of nucleotide-binding oligomerization domain (NOD)-like receptor family CARD domain containing 5 (NLRC5) in cardiac hypertrophy, and to explore the mechanism implicated in this effect Cardiac hypertrophy was induced in neonatal rat cardiac myocytes using 1 µM of angiotensin II (Ang II) for 12, 24 and 48 h. Overexpression of NLRC5 was induced in H9C2 cells, and the NLRC5 + Ang II-treated cells were exposed to SC9 and 3-methyladenine (3MA). An immunofluorescence assay was used for α-actinin staining, and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for NLRC5, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) determination. Western blot analysis was applied to measure the levels of NLRC5, microtubule-associated protein 1A/1B-light chain 3 type I (LC3I), LC3II, sequestosome 1 (p62), protein kinase B (AKT), phosphorylated Akt (pAKT), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR). The level of NLRC5 was significantly decreased after Ang II treatment in cardiomyocytes, but the levels of ANP and BNP were increased. Overexpression of NLRC5 reduced the cell size, downregulated the levels of ANP and BNP, increased LC3II / LC3I, but decreased p62 in Ang II-induced cardiomyocyte hypertrophy. In addition, the results from Western blot showed that overexpression of NLRC5 distinctly decreased the ratios of pAKT/AKT and pmTOR/mTOR in cardiomyocyte hypertrophy. SC79 and 3MA significantly downregulated the ratio of LC3I/LC3II but increased the level of p62 in NLRC5 + Ang II-treated cells. These results provide a possible novel therapeutic strategy for cardiac hypertrophy that might be useful in a clinical setting.

Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay.

PURPOSE: The recently identified agonistic autoantibodies (AAb) to the gonadotropin-releasing hormone receptor (GnRHR) are a novel investigative and therapeutic target for polycystic ovary syndrome (PCOS). In this study, we used a new cell-based fluorescence resonance energy transfer (FRET) bioassay to analyze serum GnRHR-AAb activity and examine its relationship with testosterone and proinflammatory cytokines in patients with PCOS. METHODS: Serum samples from 33 PCOS patients, 39 non-PCOS ovulatory infertile controls and 30 normal controls were tested for GnRHR-AAb activity and proinflammatory cytokines in a FRET-based bioassay and multiplex bead-based immunoassay, respectively. Correlation was analyzed using the Spearman's correlation test. RESULTS: Serum GnRHR-AAb activity was significantly higher in the PCOS patients than for the ovulatory infertile (p < 0.05) and normal (p < 0.01) controls. GnRHR-AAb were positive in 39% of PCOS patients, 10% of ovulatory infertile controls, and 0% of normal controls. PCOS IgG-induced GnRHR activation was specifically blocked by the GnRHR antagonist cetrorelix. Serum levels of proinflammatory cytokines interleukin-2, interleukin-6, interferon-γ, and tumor necrosis factor-α were significantly increased in PCOS patients compared with ovulatory infertile and normal controls (p < 0.01). Correlation analysis demonstrated positive correlations of GnRHR-AAb activity with testosterone and proinflammatory cytokine levels in the PCOS group. CONCLUSIONS: Elevated GnRHR-AAb activity, as assessed by a new FRET assay, is associated with increased testosterone and proinflammatory cytokines in PCOS, suggesting autoimmune activation of GnRHR may contribute to the pathogenesis of this common disorder.

Gonadotrophin-releasing hormone receptor autoantibodies induce polycystic ovary syndrome-like features in a rat model.

NEW FINDINGS: What is the central question of this study? Is there a causal relationship between gonadotrophin-releasing hormone (GnRH) receptor-activating autoantibodies and polycystic ovary syndrome (PCOS)? What is the main finding and its importance? Induction of GnRH receptor-activating autoantibodies in rats resulted in increased luteinizing hormone pulsatility and testosterone concentrations, disrupted oestrous cycles, increased atretic follicles, and activation of insulin signalling in the pituitary and ovary. These changes replicate those seen in humans with PCOS, suggesting that GnRH receptor-activating autoantibodies might be involved in the pathogenesis of PCOS. ABSTRACT: Gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). In the present study, we examined the impact of GnRHR-AAb on reproductive function in GnRHR-immunized female rats. All immunized rats produced high titres of GnRHR-AAb targeting a dominant epitope located in the central region of the second extracellular loop of the GnRHR. Increased pulsatile luteinizing hormone secretion and testosterone concentrations were found in immunized rats. These rats exhibited disrupted oestrous cycles, increased ovarian follicular atresia, and activation of insulin signalling in the pituitary and ovary, as indicated by increased mRNA expressions of insulin receptor substrate, phosphatidylinositol 3-kinase and glucose transporter 1. No significant changes in inflammatory cytokines were detected in the ovarian tissue. These features mimic those observed in humans with PCOS. Our findings support the concept that chronic stimulation of the GnRHR by GnRHR-AAb, with an associated increase in pituitary luteinizing hormone secretion and ovarian androgen overproduction, might represent a new aetiological mechanism for PCOS.

Autoimmune activation of the GnRH receptor induces insulin resistance independent of obesity in a female rat model.

Polycystic ovary syndrome (PCOS), a metabolic and reproductive disease, is frequently associated with type 2 diabetes. We have demonstrated activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of the gonadotropin-releasing hormone receptor (GnRHR) are present in a significant subgroup of PCOS patients. It is unclear whether GnRHR-AAb can induce peripheral tissue insulin resistance (IR) in animal models. Sixteen rats were divided equally into a GnRHR ECL2 peptide-immunized group (IMM group) and a control group (CON group). Sera GnRHR-AAb titer, luteinizing hormone (LH), and testosterone (T) were higher in IMM rats compared with CON rats. No significant difference in fasting blood glucose was observed between the two groups. However, the plasma glucose level at other time points of the IMM group was higher than that of the CON group during an intraperitoneal glucose tolerance test (IPGTT) and an insulin tolerance test (ITT) (p < 0.01). These data support the likelihood of the GnRHR-AAb induction of glucose intolerance and IR. Compared with the CON group, the IMM group showed a significant increase in insulin-stimulated phosphorylation of IRS-1 (p-IRS-1 S636/639) and a decrease in insulin-stimulated phosphorylation of Akt (p-AKT S473). Expression of the glucose transport genes including GLUT-2 in liver and GLUT-4 in white adipose tissue and skeletal muscle was significantly decreased in IMM rats compared with the CON rats. Serum levels of proinflammatory cytokines (TNF-α, IL-1α, and IL-18) were increased, while anti-inflammatory cytokines (IL-4 and IL-10) were decreased in the IMM group. Taken together, elevated GnRHR-AAb enhanced LH, hyperandrogenism, and inflammation. These changes are likely related to the observed peripheral tissue IR through the downregulation of the insulin-stimulated IRS/PI3K/Akt/Glut signaling pathway.

The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα.

Zileuton has been demonstrated to be an anti-inflammatory agent due to its well-known ability to inhibit 5-lipoxygenase (5-LOX). However, the effects of zileuton on cardiac remodeling are unclear. In this study, the effects of zileuton on pressure overload-induced cardiac remodeling were investigated and the possible mechanisms were examined. Aortic banding was performed on mice to induce a cardiac remodeling model, and the mice were then treated with zileuton 1 week after surgery. We also stimulated neonatal rat cardiomyocytes with phenylephrine (PE) and then treated them with zileuton. Our data indicated that zileuton protected mice from pressure overload-induced cardiac hypertrophy, fibrosis, and oxidative stress. Zileuton also attenuated PE-induced cardiomyocyte hypertrophy in a time- and dose-dependent manner. Mechanistically, we found that zileuton activated PPARα, but not PPARγ or PPARθ, thus inducing Keap and NRF2 activation. This was confirmed with the PPARα inhibitor GW7647 and NRF2 siRNA, which abolished the protective effects of zileuton on cardiomyocytes. Moreover, PPARα knockdown abolished the anticardiac remodeling effects of zileuton in vivo. Taken together, our data indicate that zileuton protects against pressure overload-induced cardiac remodeling by activating PPARα/NRF2 signaling.

Enhanced electrochemical oxidation of Acid Red 3R wastewater with iron phosphomolybdate supported catalyst.

Electrochemical oxidation of Acid Red 3R (AR3R) was investigated with the new catalyst of iron phosphomolybdate (FePMo12) supported on modified molecular sieves type 4 Å (4A) as packing materials in the reactor. The results of the Fourier transform infrared spectroscopy and X-ray diffraction indicated that the heteropolyanion had a Keggin structure. The optimal conditions for decolorization of simulated AR3R wastewater were as follows: current density 35 mA/cm², initial pH 4.0, airflow 0.08 m³/hour and inter-electrode distance 3.0 cm. With the addition of NaCl to the system, the decolorization efficiency increased. But Na2SO4had a negative effect on the decolorization efficiency, which was attributed to the negative salt effect. The degradation mechanisms of AR3R were also discussed in detail.

Biological catalyzed denitrification by a functional electropolymerization biocarrier modified by redox mediator.

Electropolymerization biocarriers were prepared by the electropolymerization of polypyrrole (PPy) on an active carbon felt (ACF) electrode using doping anions anthraquinone-2-sulfonate (AQS) or Na(2)SO(4). The functional electropolymerization biocarrier (ACF/PPy/AQS) with AQS was used as an immobilized redox mediator for the denitrification process. The characteristics of the electropolymerization biocarriers were analyzed by scanning electron microscope, elemental analyses, Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy. The results suggested that the denitrification efficiency increased nearly 1.5-fold with ACF/PPy/AQS (0.04 mmol L(-1) AQS) compared to the control. A linear correlation was found for the k value and the AQS concentration (C(AQS)), which was k=624.71C(AQS)+83.87 (R(2)=0.9893). The ORP value stabilized around -200 mV for the denitrification process with ACF/PPy/AQS, which was -25 mV lower than that with ACF/PPy/Na(2)SO(4). Repeated-batch operations indicated that the denitrification efficiency with ACF/PPy/AQS maintained over 90% of the original value and exhibited better catalytic activity and durability.