The prognostic value of dynamic changes in SII for the patients with STEMI undergoing PPCI.

BACKGROUND: Predicting the prognosis of primary percutaneous coronary intervention(PPCI) in ST-segment elevation myocardial infarction (STEMI) patients in the perioperative period is of great clinical significance. The inflammatory response during the perioperative period is also an important factor. This study aimed to investigate the dynamic changes in the systemic immune inflammatory index (SII) during the perioperative period of PPCI and evaluate its predictive value for in-hospital and out-of-hospital outcomes in patients with STEMI. METHODS: This retrospective study included 324 consecutive patients with STEMI who were admitted to the cardiac care unit. Blood samples were collected before PPCI, 12 h (T1), 24 h, 48 h after PPCI, the last time before hospital discharge (T2), and 1 month after hospital discharge. The SII was calculated as (neutrophils×platelets)/lymphocytes. Based on whether the primary endpoint occurred, we divided the patients into event and non-event groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors that might influence the occurrence of the primary endpoint. Dynamic curves of SII were plotted, and receiver operating characteristic (ROC) curves were drawn for each node to calculate the optimal critical value, sensitivity, and specificity to assess their predictive ability for in-hospital and out-of-hospital courses. Kaplan-Meier curves were used to analyze the differences in survival rates at different SII inflammation levels. RESULTS: High levels of SII were individually related to the occurrence of the in-hospital period and long-term outcomes during the post-operative follow-up of STEMI patients (in-hospital SII: T1:OR 1.001,95%CI 1.001-1.001, P < 0.001; SII following hospital discharge: T1M: OR 1.008,95%CI 1.006-1.010, P < 0.001). Patients with high SII levels had lower survival rates than those with low SII levels. The analysis showed that the SII 12 h after (T1) and SII 1 month (T1M) had excellent predictive values for the occurrence of in-hospital and out-of-hospital outcomes, respectively (AUC:0.896, P < 0.001; AUC:0.892, P < 0.001). CONCLUSION: There is a significant relationship between the dynamic status of SII and prognosis in patients with STEMI. This study found that the 12 h and SII 1 month affected in-hospital and out-of-hospital outcomes, respectively. Consequently, we focused on the dynamic changes in the SII.

Diagnostic value of parameters derived from planar MUGA for detecting HFpEF in coronary artery disease patients.

BACKGROUND: In recent years, heart failure with preserved ejection fraction (HFpEF) has received increasing clinical attention. To investigate the diagnostic value of diastolic function parameters derived from planar gated blood-pool imaging (MUGA) for detecting HFpEF in coronary atherosclerotic heart disease (coronary artery disease, CAD) patients. METHODS: Ninety-seven CAD patients with left ventricular ejection fraction ≥ 50% were included in the study. Based on the left ventricular end-diastolic pressure (LVEDP), the patients were divided into the HFpEF group (LVEDP ≥ 16 mmHg, 47 cases) and the normal LV diastolic function group (LVEDP < 16 mmHg, 50 cases). Diastolic function parameters obtained by planar MUGA include peak filling rate (PFR), filling fraction during the first third of diastole (1/3FF), filling rate during the first third of diastole (1/3FR), mean filling rate during diastole (MFR), and peak filling time (TPF). Echocardiographic parameters include left atrial volume index (LAVI), peak tricuspid regurgitation velocity (peak TR velocity), transmitral diastolic early peak inflow velocity (E), average early diastolic velocities of mitral annulars (average e'), average E/e' ratio. The diastolic function parameters obtained by planar MUGA were compared with those obtained by echocardiography to explore the clinical value of planar MUGA for detecting HFpEF. RESULTS: The Receiver-operating characteristic curve analysis of diastolic function parameters obtained from planar MUGA and echocardiography to detect HFpEF showed that: among the parameters examined by planar MUGA, the area under the curve (AUC) of PFR, 1/3FF, 1/3FR, MFR and TPF were 0.827, 0.662, 0.653, 0.663 and 0.809, respectively. Among the echocardiographic parameters, the AUCs for average e', average E/e' ratio, peak TR velocity, and LAVI values were 0.747, 0.706, 0.735, and 0.633. The combination of PFR and TPF showed an AUC of 0.856. PFR combined with TPF value demonstrated better predictive value than average e' (Z = 2.020, P = 0.043). CONCLUSION: Diastolic function parameters obtained by planar MUGA can be used to diagnose HFpEF in CAD patients. PFR combined with TPF was superior to the parameters obtained by echocardiography and showed good sensitivity and predictive power for detecting HFpEF.

Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a.

BACKGROUND: The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms. METHODS: Neonatal rat cardiomyocytes and Sprague-Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17ß-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium. RESULTS: Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury. CONCLUSIONS: Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD. Video Abstract.

Prevalence of cardiovascular diseases in relation to total bone mineral density and prevalent fractures: A population-based cross-sectional study.

BACKGROUND AND AIM: We aimed to explore the relationship between total BMD and prevalent fractures and the risk of CVD in a female population in the United States (US). METHODS AND RESULTS: We undertook cross-sectional analyses of a female population participating in the US National Health and Nutrition Examination Survey (NHANES). Generalized linear models and restricted cubic spline curves were used to examine the association between total BMD and CVD. Subgroup analyses were also undertaken. A total of 13,707 women were enrolled. The restricted cubic spline curve revealed a linear and negative association between total BMD and CVD. The inflection point for the curve was identified at total BMD = 1.085 g/cm2. A negative relationship between total BMD and the prevalence of individual CVDs (angina and stroke) was noted (P < 0.05). In subgroup analyses stratified by race/ethnicity, hypertension, diabetes mellitus, and physical activity, a negative association existed in women who were non-Hispanic White, without hypertension, without diabetes mellitus, and who never participated in physical activity, respectively. In subgroup analyses stratified by age, this association also differed based on age. In addition, participants without history of fracture had significant lower probability of experiencing individual CVDs (angina pectoris, heart attack, and stroke) compared with those with history of fracture. CONCLUSIONS: We revealed a reduced prevalence of CVD associated with increased total BMD in a female population in the US. CVD risk decreased significantly if total BMD >1.085 g/cm2. Additionally, fracture-free individuals had much reduced odds of developing CVD.

Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial.

AIM: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. METHODS AND RESULTS: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772). CONCLUSION: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. STUDY REGISTRATION: http://www.clinicaltrials.com; Identifier: NCT02284750.

The association between manganese exposure with cardiovascular disease in older adults: NHANES 2011-2018.

The aim of the current study was to explore possible connections between manganese exposure and the prevalence of cardiovascular disease (CVD) in older US adults. The relationship between serum manganese levels and CVD was explored in 2427 people aged 60 years and over using data from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariate linear regression analysis was performed to investigate associations between CVD risk factors and serum manganese concentration. The relationship between manganese levels and the prevalence of CVD was probed using generalized linear models and restricted cubic spline curves. Stratified subgroup analysis was subsequently constructed to rule out spurious interactions between variables and manganese. Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 0.71 (OR: 0.51; CI: 1.00), 0.70 (0.50, 0.99), and 0.49 (0.34, 0.72). In the full adjusted model, a prominent negative relationship was observed between serum manganese concentration and CVD. A restricted cubic spline curve was used to show a nonlinear negative relationship between manganese concentration and CVD. In summary, manganese levels are negatively correlated with the risk of CVD in a nation-wide study of older US adults.

One-year clinical results of the NANO registry: A multicenter, prospective all-comers registry study in patients receiving implantation of a polymer-free sirolimus-eluting stent.

OBJECTIVES: We aimed to evaluate the safety and efficacy of Nano+™ (Lepu Medical, Beijing, China) stent implantation in all-comer patients at the 1-year follow-up. BACKGROUND: The Nano+™ stent is a novel polymer-free sirolimus-eluting stent polymer that employs nanoporous stent surface technology to control drug-delivery. The Nano+™ stent is one of the most widely used drug-eluting stent (DES) in China. METHODS: A total of 2,481 consecutive patients were included in the multicenter and prospective NANO registry. In this study, the primary endpoint was target lesion failure (TLF) at 1-year follow-up, defined as a composite of cardiac death, target vessel nonfatal myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). The safety endpoint was the occurrence of definite or probable stent thrombosis (ST). RESULTS: Up to 40.2% of patients presented with acute myocardial infarction (AMI). A total of 63.9% of the 2,904 lesions were American College of Cardiology/American Heart Association (ACC/AHA) type B2 or C lesions. One-year follow-up data were available for 98.4% of patients. The 1-year rate of TLF was 3.1% with rates of 1.3, 1.8, and 0.4% for clinically driven TLR, cardiac death, and TV-MI, respectively. ST occurred in 0.4% of patients. Diabetes mellitus, AMI, left ventricular ejection fraction <40% and long lesions (>40 mm) were independent predictors of 1-year TLF. CONCLUSIONS: The 1-year clinical outcomes were excellent for Nano+™ polymer-free SES implantation in an all-comer patient population. Follow-up will be extended up to 5 years, to further elucidate the potential long-term clinical benefits. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.

Luteolin Modulates SERCA2a Leading to Attenuation of Myocardial Ischemia/ Reperfusion Injury via Sumoylation at Lysine 585 in Mice.

BACKGROUND/AIMS: The myocardial sarcoplasmic reticulum calcium ATPase (SERCA2a) is a pivotal pump responsible for calcium cycling in cardiomyocytes. The present study investigated the effect of luteolin (Lut) on restoring SERCA2a protein level and stability reduced by myocardial ischemia/reperfusion (I/R) injury. We verified a hypothesis that Lut protected against myocardial I/R injury by regulating SERCA2a SUMOylation. METHODS: The hemodynamic data, myocardial infarct size of intact hearts, apoptotic analysis, mitochondrial membrane potential (ΔΨm), the level of SERCA2a SUMOylation, and the activity and expression of SERCA2a were examined in vivo and in vitro to clarify the cardioprotective effects of Lut after SUMO1 was knocked down or over-expressed. The putative SUMO conjugation sites in mouse SERCA2a were investigated as the possible regulatory mechanism of Lut. RESULTS: Initially, we found that Lut reversed the SUMOylation and stability of SERCA2a as well as the expression of SUMO1, which were reduced by I/R injury in vitro. Furthermore, Lut increased the expression and activity of SERCA2a partly through SUMO1, thus improving ΔΨm and reducing apoptotic cells in vitro and promoting the recovery of heart function and reducing infarct size in vivo. We also demonstrated that SUMO acceptor sites in mouse SERCA2a involving lysine 585, 480 and 571. Among the three acceptor sites, Lut enhanced SERCA2a stability via lysine 585. CONCLUSIONS: Our results suggest that Lut regulates SERCA2a through SUMOylation at lysine 585 to attenuate myocardial I/R injury.

Luteolin Enhances Sarcoplasmic Reticulum Ca2+-ATPase Activity through p38 MAPK Signaling thus Improving Rat Cardiac Function after Ischemia/Reperfusion.

BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R. The phosphorylation of p38 and phospholamban (p-PLB), the levels and activity of SERCA2a and the levels of proteins related to apoptosis were measured. Apoptotic cells were assessed using the TUNEL assay. Single-cell shortening, Ca2+ transients, and the decay of the mitochondrial membrane potential (Δψm) were detected. RESULTS: The p38 MAPK pathway was activated during the I/R process, and inhibiting it with SB203580 promoted p-PLB, which enhanced the activity of SERCA2a and relieved the calcium overload to promote the recovery of the Δψm and reduce cardiomyocyte apoptosis in I/R. Luteolin also suppressed the activation of the p38 MAPK pathway and showed cardioprotective effects during I/R injury. CONCLUSIONS: We conclude that luteolin enhances SERCA2a activity to improve systolic/diastolic function during I/R in rat hearts and cardiomyocytes by attenuating the inhibitive effects of the p38 pathway on p-PLB.

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy.

BACKGROUND: Our previous studies demonstrated that luteolin, which is rich in flavones, has various biological properties and can exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. However, its effect on ox-LDL-induced macrophage lipid accumulation and apoptosis has not been revealed. AIMS: This study aimed to explore the role of luteolin in ox-LDL-induced macrophage-derived foam cell formation and apoptosis and to delineate the underlying mechanism. METHODS: Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (50 µg/ml) for 24 h and then pretreated with 25 µM luteolin for another 24 h. The effects of luteolin on lipid accumulation in RAW264.7 cells induced by ox-LDL were assayed using Oil red O staining and high performance liquid chromatography (HPLC). Apoptosis was confirmed by acridine orange/ethidium bromide (AO/EB) staining, flow cytometric analysis and the TUNEL assay. Immunofluorescence, Western blot and monodansylcadaverine (MDC) staining analyses were then used to further investigate the molecular mechanisms by which luteolin protects macrophages from ox-LDL-induced foam cell formation and apoptosis. 3-Methyladenine (3-MA), an autophagy inhibitor, was used as a positive control. RESULTS: Treatment with 25 µM luteolin not only significantly attenuated ox-LDL-induced macrophage lipid accumulation but also decreased the apoptotic rate of RAW264.7 cells, the number of TUNEL-positive macrophages and the expression of Bax, Bak, cleaved caspase-9 and cleaved caspase-3. In addition, luteolin pretreatment significantly increased autophagosome formation and Beclin-1 activity, thus increasing the ratio of LC3-II/LC3-I. Moreover, these effects were abolished by 3-MA. CONCLUSIONS: Taken together, these results highlight that luteolin treatment attenuates foam cell formation and macrophage apoptosis by promoting autophagy and provide new insights into the molecular mechanism of luteolin and its therapeutic potential in the treatment of atherosclerosis.

Lentiviral-mediated overexpression of Akt1 reduces anoxia-reoxygenation injury in cardiomyocytes.

Activated PI3K/Akt signalling exerts a protective effect after myocardial ischemia by phosphorylating various substrates; however, the precise mechanism by which this occurs remains to be elucidated. We have constructed the recombinant lentiviral vector pLVX-Akt1-EGFP- 3FLAG (LV-Akt1) to determine the efficiency of LV-Akt1 infection, explore the protective role of Akt1, and investigate the possible mechanism by which Akt1 signalling acts during anoxia/reoxygenation (A/R) of cardiomyocytes in primary culture. Akt1 gene transfection increased cardiomyocyte pulsation, reduced cell mortality, and decreased the concentration of lactate dehydrogenase (LDH) in myocardial cells supernatants. Akt1 transfection increased the levels of intracellular p-Akt, enhanced the expression of the anti-apoptosis protein Bcl-2, and reduced that of the apoptosis protein Bax (thereby increasing the Bcl-2/Bax ratio), and caused some increase in hypoxia-inducible factor1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression after A/R. The protective role of Akt1 was partly suppressed by adding a phosphoinositide 3-kinase/Akt inhibitor (LY294002). In conclusion, LV-Akt1 was successfully constructed and neonatal rat cardiomyocytes were transfected efficiently. Akt1 overexpression significantly reduced A/R injury in cardiomyocytes, and this could be related to its effects on various targets of the PI3K/Akt signalling pathway, such as Bcl-2, Bax, HIF-1α and VEGF.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Luteolin inhibits inflammatory responses via p38/MK2/TTP-mediated mRNA stability.

Luteolin (Lut) is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. The purposes of this study were to observe the inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in bone marrow macrophages (BMM) by Lut, and to examine whether this inhibition involves p38/MK2/TTP-mediated mRNA stability. Lut suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner according to enzyme-linked immunosorbent assay (ELISA) analysis. Lut also shortened the half-lives of the TNF-α and IL-6 mRNAs according to real-time PCR analysis. Western blots were performed to assess the activation of p38 and MK2 as well as the expression of TTP. The results indicated that Lut inhibited p38 and MK2 phosphorylation while promoting TTP expression. These results suggest that the anti-inflammatory effects of Lut are partially mediated through p38/MK2/TTP-regulated mRNA stability.

SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury.

BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION: I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.

Development and validation of a risk nomogram model for predicting pulmonary hypertension in patients with stage 3-5 chronic kidney disease.

OBJECTIVES: The occurrence of pulmonary arterial hypertension (PAH) can greatly affect the prognosis of patients with chronic kidney disease (CKD). We aimed to construct a nomogram to predict the probability of PAH development in patients with stage 3-5 CKD to guide early intervention and to improve prognosis. METHODS: From August 2018 to December 2021, we collected the data of 1258 patients with stage 3-5 CKD hospitalized at the Affiliated Hospital of Xuzhou Medical University as a training set and 389 patients hospitalized at Zhongda Hospital as a validation set. These patients were divided into PAH and N-PAH groups with pulmonary arterial systolic pressure ≥ 35 mmHg as the cutoff. The results of univariate and multivariate logistic regression analyses were used to establish the nomogram. Then, areas under the receiver operating characteristic curve (AUC-ROCs), a calibration plot, and decision curve analysis (DCA) were used to validate the nomogram. RESULTS: The nomogram included nine variables: age, diabetes mellitus, hemoglobin, platelet count, serum creatinine, left ventricular end-diastolic diameter, left atrial diameter, main pulmonary artery diameter and left ventricular ejection fraction. The AUC-ROCs of the training set and validation set were 0.801 (95% confidence interval (CI) 0.771-0.830) and 0.760 (95% CI 0.699-0.818), respectively, which showed good discriminative ability of the nomogram. The calibration diagram showed good agreement between the predicted and observed results. DCA also demonstrated that the nomogram could be clinically useful. CONCLUSION: The evaluation of the nomogram model for predicting PAH in patients with CKD based on risk factors showed its ideal efficacy. Thus, the nomogram can be used to screen for patients at high risk for PAH and has guiding value for the subsequent formulation of prevention strategies and clinical treatment.

Preliminary assessment of cardiotoxicity in chimeric antigen receptor T cell therapy: a systematic review and meta-analysis.

As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our study aimed to preliminarily assess the prevalence of cardiotoxicity after CAR T cell treatment using a systematic review and meta-analysis. PubMed, Embase, Web of Science, and Cochrane databases were searched for potentially relevant studies. All types of relevant clinical studies were screened and assessed for risk bias. In most instances, random-effect models were used for data analysis, and heterogeneity between studies was evaluated. Standard quality assessment tools were used to assess quality. The study was registered with PROSPERO (CRD42022304611). Eight eligible studies comprising 3567 patients, including seven observational studies and one controlled study, were identified. The incidence of cardiovascular events was 16.7% [95% confidence interval (CI) 0.138-0.200, P < 0.01)]. Arrhythmia was the most common disorder, with an incidence of 6.5% (95% CI 0.029-0.115, P < 0.01). The occurrence of cardiotoxicity was associated with cytokine release syndrome (CRS), with a prevalence of 18.7% (95% CI 0.107-0.315, P < 0.01). Moreover, such adverse reactions were more common when CRS > 2 (OR = 0.07, 95% CI 0.02-0.29, P < 0.01). The risk of cardiotoxicity was not notably higher in patients receiving CAR T cell therapy than in those receiving traditional anticancer treatment. However, sufficient attention should be paid to this. And further evidence from large-scale clinical trials are needed.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis.

INTRODUCTION: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. METHODS: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. RESULTS: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. CONCLUSION: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

Development and Validation of a Nomogram for Predicting All-Cause Mortality in Patients with Hemodialysis Having Pulmonary Hypertension.

INTRODUCTION: Patients with end-stage renal disease receiving hemodialysis (HD) have a high morbidity and mortality rate associated with pulmonary hypertension (PH). A nomogram was developed to predict all-cause mortality in HD patients with PH. In this study, we aimed to validate the usefulness of this nomogram. METHODS: A total of 274 HD patients with PH were hospitalized at the Affiliated Hospital of Xuzhou Medical University between January 2014 and June 2019 and followed up for 3 years. Echocardiography detected PH when the peak tricuspid regurgitation velocity (TRV) was more than 2.8 m/s. To evaluate the all-cause mortality for long-term HD patients with PH, Cox regression analysis was performed to determine the factors of mortality that were included in the prediction model. Next, the area under the receiver-operating characteristic curve (AUC-ROC) was used to assess the predictive power of the model. Calibration plots and decision curve analysis (DCA) were used to assess the accuracy of the prediction results and the clinical utility of the model. RESULTS: The all-cause mortality rate was 29.20% throughout the follow-up period. The nomogram comprised six commonly available predictors: age, diabetes mellitus, cardiovascular disease, hemoglobin, left ventricular ejection fraction, and TRV. The 1-year, 2-year, and 3-year AUC-ROC values were 0.842, 0.800, and 0.781, respectively. The calibration curves revealed excellent agreement with the nomogram, while the DCA demonstrated favorable clinical practicability. CONCLUSION: The first developed nomogram for predicting all-cause mortality in HD patients with PH could guide clinical decision-making and intervention planning.

Development and Validation of a Nomogram Model for Predicting the Risk of Readmission in Patients with Heart Failure with Reduced Ejection Fraction within 1 Year.

The high incidence of readmission for patients with reduced ejection fraction heart failure (HFrEF) can seriously affect the prognosis. In this study, we aimed to build a simple predictive model to predict the risk of heart failure (HF) readmission in patients with HFrEF within one year of discharge from the hospital. This retrospective study enrolled patients with HFrEF evaluated in the Heart Failure Center of the Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2020. The patients were allocated into the readmission or nonreadmission group, according to whether HF readmission occurred within 1 year of hospital discharge. Subsequently, all patients were randomly divided into training and validation sets in a 7 : 3 ratio. A nomogram was established according to the results of univariate and multivariate logistic regression analysis. Finally, the area under the receiver operating characteristic curve (AUC-ROC), calibration plot, and decision curve analysis (DCA) were used to validate the nomogram. Independent risk factors for HF readmission of patients with HFrEF within 1 year of hospital discharge were as follows: age, body mass index, systolic blood pressure, diabetes mellitus, left ventricular ejection fraction, and angiotensin receptor-neprilysin inhibitors. The AUC-ROC of the training and validation sets were 0.833 (95% confidence interval (CI): 0.793-0.866) and 0.794 (95% CI: 0.727-0.852), respectively, which have an excellent distinguishing ability. The predicted and observed values of the calibration curve also showed good consistency. DCA also confirmed that the nomogram had good clinical value. In conclusion, we constructed an accurate and straightforward nomogram model for predicting the 1-year HF readmission risk in patients with HFrEF. This nomogram can guide early clinical intervention and improve patient prognosis.

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis.

INTRODUCTION: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF. METHODS: The microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein-protein interaction (PPI) network, miRNA- messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA-mRNA network. RESULTS: Thirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen "hub" genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-ß and Hippo signaling pathway. CONCLUSION: We identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-ß and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.