FNDC5/irisin ameliorates bone loss of type 1 diabetes by suppressing endoplasmic reticulum stress­mediated ferroptosis.

BACKGROUND: Ferroptosis is known to play a crucial role in diabetic osteopathy. However, key genes and molecular mechanisms remain largely unclear. This study aimed to identify a crucial ferroptosis-related differentially expressed gene (FR-DEG) in diabetic osteopathy and investigate its potential mechanism. METHODS: We identified fibronectin type III domain-containing protein 5 (FNDC5)/irisin as an essential FR-DEG in diabetic osteopathy using the Ferroptosis Database (FerrDb) and GSE189112 dataset. Initially, a diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ), followed by intraperitoneal injection of irisin. MC3T3-E1 cells treated with high glucose (HG) were used as an in vitro model. FNDC5 overexpression plasmid was used to explore underlying mechanisms in vitro experiments. Femurs were collected for micro-CT scan, histomorphometry, and immunohistochemical analysis. Peripheral serum was collected for ELISA analysis. Cell viability was assessed using a CCK-8 kit. The levels of glutathione (GSH), malondialdehyde (MDA), iron, reactive oxygen species (ROS), and lipid ROS were detected by the corresponding kits. Mitochondria ultrastructure was observed through transmission electron microscopy (TEM). Finally, mRNA and protein expressions were examined by quantitative real-time PCR (qRT-PCR) and western blot analysis. RESULTS: The expression of FNDC5 was found to be significantly decreased in both in vivo and in vitro models. Treatment with irisin significantly suppressed ferroptosis and improved bone loss. This was demonstrated by reduced lipid peroxidation and iron overload, increased antioxidant capability, as well as the inhibition of the ferroptosis pathway in bone tissues. Furthermore, in vitro studies demonstrated that FNDC5 overexpression significantly improved HG-induced ferroptosis and promoted osteogenesis. Mechanistic investigations revealed that FNDC5 overexpression mitigated ferroptosis in osteoblasts by inhibiting the eukaryotic initiation factor 2 alpha (eIF2α)/activated transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) pathway. CONCLUSIONS: Collectively, our study uncovered the important role of FNDC5/irisin in regulating ferroptosis of diabetic osteopathy, which might be a potential therapeutic target.

Optimized gated a SPECT-derived myocardial salvage index: its prognostic significance in predicting major adverse cardiac events following acute myocardial infarction percussion.

PURPOSE: Estimate myocardial salvage index (MSI) using a single-gated Single-Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (GSMPI) early after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) and compare its predictive value with the traditional method especially for post-PCI left ventricular ejection fraction (LVEF) improvement and major adverse cardiac events (MACEs). METHODS: GSMPI was performed in 62 patients with AMI early after PCI (3-10 days). The MSI and the conventional parameters were obtained, including total perfusion deficit, LVEF, peak ejection rate (PER), and peak filling rate (PFR). The new calculation method (scoring evaluation method means the extent of abnormality is the percentage of the total scores of abnormal segments divided by the sum of the maximum scores of all myocardial segments using 4-point and 5-point scale semi-quantitative scoring method) and the reference method (number evaluation method means the extent of abnormality is the percentage of the number of abnormal segments divided by the total number of myocardial segments) were applied to acquire the MSI. We compared the predictive ability of the 2 methods based on the area under the receiver operating characteristic curve for LVEF improvement 6 months after PCI using MSI. The Kaplan-Meier method was used for depicting survival curves for predicting MACEs by the 2 methods. Cox proportional-hazards regression was applied to confirm the independent predictors of MACEs. RESULTS: The MSI obtained by the new method indicated stronger prognostic significance in LVEF improvement [area under the curve (AUC): 0.793, 95% confidence interval (CI) 0.620-0.912, P < .001] compared with the reference method (AUC: 0.634, 95%CI 0.452-0.792, P = .187). Delong's test revealed a statistically significant difference in AUCs between the 2 methods (P < .05, 95%CI 0.003-0.316). The diagnostic value of the scoring evaluation method was higher than that of the number evaluation method. The Cox prevalence of MACEs was substantially higher in the < median MSI group than in the ≥ median MSI group (hazard ratio: 0.172; 95% CI 0.041-0.724; P < .05] using the new method, whereas no considerable differences were observed between the 2 groups using the reference method (P = .12). Further, the multivariate Cox regression analysis revealed that MSI was an independent indicator for predicting MACEs (P < .05). CONCLUSION: The MSI obtained from a simple GSMPI early after PCI, using the scoring evaluation method, was a reliable prognostic indicator for predicting LVEF improvement and MACEs in AMI. It remarkably improved the prognostic value compared with the previous reference methods.

DAP1 regulates osteoblast autophagy via the ATG16L1-LC3 axis in Graves' disease-induced osteoporosis.

OBJECTIVE: This study aimed to uncover a critical protein and its mechanisms in modulating autophagy in Graves' disease (GD)-induced osteoporosis (OP). METHODS: We discovered the target protein, death-associated protein 1 (DAP1), using bone proteomics analysis. Furthermore, genetic overexpression and knockdown (KD) of DAP1 in bone and MC3T3-E1 cells revealed DAP1 effects on autophagy and osteogenic markers, and autophagic vacuoles in cells were detected using transmission electron microscopy and the microtubule-associated protein 1 light chain 3 alpha (MAP1LC3/LC3) dual fluorescence system. An autophagy polymerase chain reaction (PCR) array kit was used to identify the key molecules associated with DAP1-regulated autophagy. RESULTS: DAP1 levels were significantly higher in the bone tissue of GD mice and MC3T3-E1 cells treated with triiodothyronine (T3). DAP1 overexpression reduced LC3 lipidation, autophagic vacuoles, RUNX family transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in MC3T3-E1 cells, whereas DAP1 KD reversed these changes. In vivo experiments revealed that GD mice with DAP1 KD had greater bone mass than control mice. DAP1-overexpressing (OE) cells had lower levels of phosphorylated autophagy-related 16-like 1 (ATG16L1) and LC3 lipidation, whereas DAP1-KD cells had higher levels. CONCLUSIONS: DAP1 was found to be a critical regulator of autophagy homeostasis in GD mouse bone tissue and T3-treated osteoblasts because it negatively regulated autophagy and osteogenesis in osteoblasts via the ATG16L1-LC3 axis.

A five-parameter score for predicting saphenous vein graft degenerative and/or occlusive disease in recurring ischemic symptoms after one year post coronary artery bypass grafting.

BACKGROUND: The recurrence rate of ischemic symptoms after coronary artery bypass grafting (CABG) is increasing in recent years. How to prevent and treat saphenous vein graft disease (SVGD [symptomatic ⩾50% stenosis in at least one Saphenous vein graft]) has been a clinical challenge to date. Different pathogenesis may exist in SVGD of different periods. There are currently few available scores for estimating the risk of SVGD after one year post CABG. OBJECTIVE: We sought to develop and validate a simple predictive clinical risk score for SVGD with recurring ischemia after one year post CABG. METHODS AND RESULTS: This was a cross-sectional study and the results were validated using bootstrap resampling on a separate cohort. A nomogram and risk scoring system were developed based on retrospective data from a training cohort of 606 consecutive patients with recurring ischemia >1 year after CABG. Logistic regression model was used to find the predictive factors and to build a nomogram. To assess the generalization, models were validated using bootstrap resampling and an external cross-sectional study of 187 consecutive patients in four other hospitals. In multivariable analysis of the primary cohort, native lesion vessel number, SVG age, recurring ischemia type, very low-density lipoprotein level, and left ventricular end-diastolic diameter were independent predictors. A summary risk score was derived from nomogram, with a cut-off value of 15. In internal and external validation, the C-index was 0.86 and 0.82, indicating good discrimination. The calibration curve for probability of SVGD showed optimal agreement between actual observations and risk score prediction. CONCLUSION: A simple-to-use risk scoring system based on five easily variables was developed and validated to predict the risk of SVGD among patients who recurring ischemia after one year post CABG. This score may be useful for providing patients with individualized estimates of SVGD risk.

Reporting and methodological quality of systematic reviews of DPP-4 inhibitors for patients with type 2 diabetes mellitus: an evidence-based mapping.

AIMS: To evaluate the reporting and methodological quality of relevant systematic reviews (SRs) and meta-analyses (MAs) on Dipeptidyl peptidase-4 inhibitors (DPP-4I) for Type 2 diabetes mellitus (T2DM). METHODS: Relevant SRs and MAs on T2DM and DPP-4I published between 2017 and November 2021 were retrieved from PubMed, Embase, Cochrane Library, Web of Science, VIP, CNKI, CBM, and WanFang databases. Two independent reviewers performed the search, selection, and data extraction. The reporting and methodological quality of the reviewers was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) tools. The relationship between reporting and methodological quality score was assessed with the Spearman correlation test. RESULTS: Twenty-one studies involving 151,715 participants were included in the study. This overview showed that DPP-4I was safer and more efficacious than other anti-hyperglycemic drugs (OADs) in treating T2DM. The methodological quality of one SR was low, while the rest were very low. Thus, refinements are needed in the quality of protocol and registration information, a complete search strategy, the summary of the evidence, the listing of excluded studies, assessing the potential impact of risk of bias in RCTs, and discussing the RoB on MA results, and the funding of RCTs need improvement for generating SR. In addition, the reporting and methodological quality scores were moderately correlated (rS = 0.66, P = 0.001). CONCLUSIONS: DPP-4I is safer and more efficacious than OADs in treating T2DM. However, the reporting and methodological quality of the related SRs was unsatisfactory. Therefore, PRISMA and AMSTAR 2 analyses should be followed to enhance the overall quality of future SRs.

Long-term outcomes of 316 patients with STEMI following coronary stent implantation.

BACKGROUND: Stent thrombosis (ST)-related ST-segment elevation myocardial infarction (STEMI) has very high mortality and poor prognosis. With the extensive construction of the chest pain center in China, the question arises as to whether these special patients will benefit. METHODS: From January 2015 to February 2018, 316 patients with STEMI admitted to the coronary care unit (CCU) of Tianjin Chest Hospital after coronary stent implantation were enrolled in this retrospective study. All patients underwent coronary angiography. According to whether STEMI was due to ST, these patients were divided into either a ST group (n=247) or a non-ST group (n=69). The in-hospital mortality and major adverse cardiac events (MACEs), including all-cause mortality, re-ST, target vessel revascularization (TVR), and acute myocardial infarction (AMI) within the 1-year follow-up were compared between the two groups. RESULTS: 78% of cases of STEMI following coronary stent implantation were caused by ST. The in-hospital mortality of the ST group was 0.8% and that of the non-ST group was 1.4% (P>0.05). Forty-two cases had MACEs in the 1-year follow-up, with a higher incidence in the ST group compared to the non-ST group (15.4% vs. 5.8%, P=0.038). The Kaplan-Meier survival analysis showed a lower 1-year event free survival (EFS) in the ST group compared to the non-ST group (84.6% vs. 94.2%, P=0.035). Age over 80-years-old, hypertension, diabetes, hypercholesterolemia, and family history of coronary artery disease (CAD) were all independent risk factors for MACE. CONCLUSION: ST is the leading cause of STEMI in patients following coronary stent implantation. There was no significant difference in mortality between the ST group and the non-ST group during hospitalization, with a worse prognosis in the ST group during the 1-year follow-up.

Latent class cluster analysis of knowledge on acute myocardial infarction in community residents: a cross-sectional study in Tianjin, China.

OBJECTIVE: Public knowledge of early onset symptoms and risk factors (RF) of acute myocardial infarction (AMI) is very important for prevention, recurrence and guide medical seeking behaviours. This study aimed to identify clusters of knowledge on symptoms and RFs of AMI, compare characteristics and the awareness of the need for prompt treatment. DESIGN: Multistage stratified sampling was used in this cross-sectional study. Latent GOLD Statistical Package was used to identify and classify the respondent subtypes of the knowledge on AMI symptoms or modifiable RFs. Multivariable logistic regression was performed to identify factors that predicted high knowledge membership. PARTICIPANTS: A structured questionnaire was used to interview 4200 community residents aged over 35 in China. 4122 valid questionnaires were recovered. RESULTS: For AMI symptoms and RFs, the knowledge levels were classified into two or three distinct clusters, respectively. 62.7% (Symptom High Knowledge Cluster) and 39.5% (RF High Knowledge Cluster) of the respondents were able to identify most of the symptoms and modifiable RFs. Respondents who were highly educated, had higher monthly household income, were insured, had regular physical examinations, had a disease history of AMI RFs, had AMI history in immediate family member or acquaintance or had received public education on AMI were observed to have higher probability of knowledge on symptoms and RFs. There was significant difference in awareness of the prompt treatment in case of AMI occurs among different clusters. 'Calling an ambulance' was the most popular option in response of seeing others presenting symptoms of AMI. CONCLUSIONS: A moderate or relatively low knowledge on AMI symptoms and modifiable RFs was observed in our study. Identification of Knowledge Clusters could be a way to detect specific targeted groups with low knowledge of AMI, which may facilitate health education, further reduce the prehospital delay in China and improve patient outcomes.

The Relevance of Interventional Time and Clinical Outcomes in Patients with NSTEMI Based on the GRACE Score.

Objective: To investigate the relevance between interventional time and clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients of different risk stratifications, which were divided into different groups according to GRACE scores and the time from admission to percutaneous coronary intervention (PCI). Method: Patients were grouped according to the GRACE score and the time from admission to intervention therapy. The Cox multivariate risk regression model was used to analyze the correlation between the GRACE score and the time from admission to intervention therapy with major adverse cardiovascular events (MACEs). Cox interactive item regression was also used to investigate the correlation between the time of intervention therapy and GRACE risk stratification with clinical outcomes and to evaluate the efficacy of intervention therapy in different risk stratifications of patients with NSTEMI. Results: Interactive item Cox regression analysis and subgroup analysis show that high-risk NSTEMI patients with a GRACE score > 140 points and the time from admission to intervention < 24 h (p = 0.0004) and 24-72 h (p = 0.0143) have interactive effects on the impact of the MACE event with the reference of intervention time > 72 h and GRACE score < 108 points. The time from admission to intervention < 24 h is an independent protective factor for the occurrence of MACE events (HR = 0.166, 95% CI 0.052-0.532, p = 0.0025). Middle-risk patients with NSTEMI with a GRACE score of 109-140 points and the time from admission to intervention < 24 h (p = 0.0370) and 24-72 h (p = 0.0471) have an interactive effect on the impact of MACE. The time from admission to intervention > 72 h is an independent protective factor for the occurrence of MACE (HR = 0.201, 95% CI 0.045-0.897, p = 0.0355). Conclusion: The time from admission to intervention < 24 h could effectively reduce the risk of MACE events within 1 year in high-risk patients with NSTEMI (GRACE score > 140 points); the time from admission to intervention > 72 h can reduce the risk of MACE events within 1 year in low-risk patients with NSTEMI (GRACE score ≤ 108 points).

Electrocardiographic patterns predict the presence of collateral circulation and in-hospital mortality in acute total left main occlusion.

BACKGROUND: Data on the clinical characteristics, electrocardiogram (ECG) findings and outcomes of patients with acute myocardial infarction (AMI) due to total unprotected left main (ULM) artery occlusion is limited. METHODS: Between 2009 and 2021, 44 patients with AMI due to total ULM occlusion underwent primary percutaneous coronary intervention (PCI) at our institution. The ECG, collateral circulation, clinical and procedural characteristics, and in-hospital mortality were retrospectively evaluated. RESULTS: Twenty five patients presented with shock and 18 patients had in-hospital mortality. Nineteen patients presented with ST-segment elevation myocardial infarction (STEMI), while 25 presented with non-ST-segment elevation myocardial infarction (NSTEMI). ST-segment elevation (STE) in I and STEMI were associated with the absence of collateral circulation, while STE in aVR was associated with its presence. In the NSTEMI group, patients with STE in both aVR and aVL showed more collateral filling of the left anterior descending coronary artery (LAD) territory, while patients with STE in aVR showed more collateral filling of the LAD and the left circumflex artery territory. Compared with total ULM occlusion, patients with partial ULM obstruction presented with more STE in aVR, less STE in aVR and aVL, and less STEMI. Shock, post-PCI TIMI 0-2 flow, non-STE in aVR, STEMI, and STE in I predicted in-hospital mortality. STEMI and the absence of collateral flow were significantly associated with shock. CONCLUSIONS: STE in the precordial leads predicted the absence of collateral circulation while STE in aVR and STE in both aVR and aVL predicted different collateral filling territories in ULM occlusion. STE in I, non-STE in aVR, and STEMI predicted in-hospital mortality in these patients.

Prognostic value of PCSK9 levels in patients with non-ST elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).

BACKGROUND: The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in predicting major adverse cardiovascular events (MACEs) in Non-ST elevation myocardial infarction (NSTEMI) patients is still an open question, and the PCSK9 concentration of clinical usefulness remains unknown in guiding treatment. METHODS AND RESULTS: A total of 272 patients with NSTEMI were included in our prospective observational cohort study. Patients were followed up for 1 year. Their baseline plasma PCSK9 levels were determined by enzyme-linked immunosorbent assay. Patients were divided into high, medium, and low PCSK9 groups. All patients followed up for the occurrence of MACEs and received PCI therapy after admission. The associations of PCSK9 with MACEs were evaluated. The results showed that the incidence of composite MACEs was greater at higher concentrations of PCSK9. PCSK9 level was related to the level of lipoproteins, high-sensitivity C-reactive protein (hs-CRP), platelet volume distribution width, and D-Dimer. There was also a statistically significant correlation between PCSK9 concentrations and the GRACE score. The Kaplan-Meier curves showed that patients with high PCSK9 level had lower event-free survival rate. The survival analysis indicated high level of PCSK9-predicted MACEs independently. Subgroup analysis demonstrated that the prognostic value of high PCSK9 level was greater for patients classified by the GRACE score as high risk. CONCLUSION: In an NSTEMI setting, the concentration of PCSK9 is associated with hypercoagulability and hyperinflammation. High levels of PCSK9 independently predict future MACEs in patients with NSTEMI, particularly those classified by the GRACE score as high risk.

Effects of Evolocumab Added to Moderate-Intensity Statin Therapy in Chinese Patients With Acute Coronary Syndrome: The EMSIACS Trial Study Protocol.

Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the "Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome" (EMSIACS) is conducted. Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment. Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects' LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over. Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.

The clinical features and prognosis of type 4C myocardial infarction in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Type 4C myocardial infarction (MI) is a special type of myocardial infarction related to restenosis without thrombosis. There is a lack of relevant data on this new classification of acute MI (AMI). This study set out to examine the prognosis and treatment of type 4C MI in patients with non-ST-segment elevation MI (NSTEMI). METHODS: With reference to the NSTEMI cohort study database, we enrolled 1,032 cases of type 1 MI and 42 cases of type 4C MI from the period January 01, 2018 to August 31, 2018. All cases were followed up for 1 year. The outcome was major cardiovascular adverse events (including all-cause deaths, nonfatal MI, heart failure necessitating hospitalization, uncontrollable angina pectoris, and revascularization of the target vessels). Risk ratios (RR) were calculated using the generalized linear model. Cox multivariate analysis was performed to analyze the prognostic effects of drug-coated balloon (DCB) angioplasty or drug-eluting stent (DES) implantation in patients with type 4C MI. RESULTS: Compared with type 1 MI, type 4C MI was associated with a higher incidence of major adverse cardiovascular events (MACEs) [21.43% vs. 5.14%; adjusted RR: 3.725, 95% confidence interval (CI): 1.937-7.164]. Type 4C MI also showed a higher 1-year mortality rate than type 1 MI (7.14% vs. 1.55%; unadjusted RR: 4.607, 95% CI: 1.395-15.212). However, after adjusting for covariates, no statistical difference was noted (adjusted RR: 2.515, 95% CI: 0.768-8.233). Multiple adjustments to the Cox multivariate models revealed that neither DCB nor DES affected the clinical outcomes. CONCLUSIONS: Type 4C MI has a poorer prognosis than type 1 MI. DCB angioplasty and DES implantation show similar efficacy in the treatment of type 4C MI.

Intracoronary pressure gradient measurement in acute myocardial infarction patients with the no-reflow phenomenon during primary percutaneous coronary intervention.

BACKGROUND: Various experimental and clinical studies have reported on coronary microcirculatory dysfunction ("no-reflow" phenomenon). Nevertheless, pathogenesis and effective treatment are yet to be fully elucidated. This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow. METHODS: From September 1st, 2018 to June 30th, 2019, intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit, Tianjin Chest Hospital, respectively in no-reflow arteries (no-reflow group) and arteries with thrombolysis in myocardial infarction-3 flow (control group). At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back. The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure. Comparison between groups was made using the Student t test, Mann-Whitney U-test or Chi-square test, as appropriate. RESULTS: Intracoronary pressure in 33 no-reflow group and 26 in control group were measured. The intracoronary forward systolic pressure gradient was -1.3 (-4.8, 0.7) and 3.8 (0.8, 8.8) mmHg in no-reflow group and control group (Z = -3.989, P < 0.001), respectively, while the forward diastolic pressure gradient was -1.0 (-3.2, 0) and 4.6 (0, 16.5) mmHg in respective groups (Z = -3.851, P < 0.001). Moreover, the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication (Z = -3.668, P < 0.001 in systolic pressure gradient and Z = -3.530, P < 0.001 in diastolic pressure gradient). CONCLUSIONS: No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries. Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov (No. NCT03600259).

Inflammatory and Hematological Indices as Simple, Practical Severity Predictors of Microdysfunction Following Coronary Intervention: A Systematic Review and Meta-Analysis.

C-reactive protein (CRP) and high-sensitivity CRP (hsCRP), along with a series of hematological indices, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), platelet distribution width (PDW), and red blood cell distribution width (RDW), are regarded to be related to the incidence of no-reflow or slow flow. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to August 24, 2019. A total of 21 studies involving 7403 patients were included in the meta-analysis. Pooled analysis results revealed patients with higher hsCRP (odds ratio [OR] = 1.03, 95% confidence interval [CI], 1.01-1.05, P = .006), hsCRP (OR = 1.04, 95% CI: 1.0-1.08, P = .012), NLR (OR = 1.23, 95% CI: 1.11-1.37, P < .0001), PLR (OR = 1.13, 95% CI: 1.07-1.20, P < .0001), and MPV (OR = 2.13, 95% CI: 1.57-2.90, P < .0001) all exhibited significantly higher no-reflow incidence, but there was no significant association between no-reflow risk and RDW or PDW. Patients with higher CRP/hsCRP also performed higher rate of slow flow (OR = 1.06, 95% CI: 1.01-1.11, P = .018). Preangiographic CRP/hsCRP could independently predict no-reflow and slow flow. Moreover, some hematological indices are associated with no-flow.

Percutaneous coronary intervention assisted by invasive mechanical ventilation and intra-aortic balloon pump for acute myocardial infarction with cardiogenic shock: Retrospective cohort study and meta-analyses.

There is little evidence to recommend the optimal invasive mechanical ventilation (IMV) modes and ideal positive end-expiratory pressure stress levels for acute myocardial infarction-cardiogenic shock (AMI-CS) patients. The aim of this study was to compare the mortality outcome in patients with AMI-CS who were treated with percutaneous coronary intervention (PCI) assisted by intra-aortic balloon pump (IABP) + IMV with historical controls. From January 1, 2016 to June 1, 2017, 60 patients were retrospectively enrolled at Tianjin Chest Hospital. Out of these, 88.3% of patients achieved thrombolysis in myocardial infarction (TIMI) flow 3 after PCI. The all-cause mortality rate in-hospital and at 1 year was 25% (95% CI: 0.14-0.36) and 33.9% (0.22-0.46), respectively. A systematic review followed by meta-analysis was performed with four historical studies of patients treated by PCI + IMV with partial IABP, which found an in-hospital mortality rate of 66.0% (95% CI: 0.62-0.71). Recently, a meta-analysis of patients receiving PCI + IABP with partial IMV showed that the 1 year mortality rate was 52.2% (95% CI: 0.47-0.58). In Cox regression analysis of patient data from the current study, lactic acid level ≥4.5 mmol/L, hyperuricemia, and TIMI flow <3 were independent predictors of death at 1 year. All-cause mortality, in-hospital and at 1 year, in patients with AMI-CS treated with PCI + IABP and IMV was lower than in those treated with PCI + partial IABP or IMV. Larger, longer-term direct comparisons are warranted.

Prediction of Major Adverse Cardiovascular Events and Slow/No-Reflow by Virtual Histology Imaging After Percutaneous Interventions on Saphenous Vein Grafts.

Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and usually treated by percutaneous coronary intervention (PCI). In this prospective cohort study, we performed virtual histology-intravascular ultrasound to investigate whether plaque composition and morphological characteristics were associated with post-PCI major adverse cardiac events (MACEs) and slow/no-reflow in patients with SVGD. Patients (n = 90) were studied (76.7% men, mean age 64.9 ± 8.2 years and mean duration of SVG 8.0 ± 3.6 years). There were 77.8% lesions with a plaque burden of at least 70%; 18 MACE incidences accumulated in 14 patients over 12 months post-PCI and slow/no-reflow was observed in 12 patients. On adjusted multivariate analysis, lesion length (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 1.01-1.08]); age of CABG (HR = 1.51 [95% CI: 1.11-2.05], and absolute necrotic core (NC) area (HR = 8.04 [95% CI: 1.86-34.73]) were independently associated with MACEs. Factors independently associated with slow/no-reflow post-PCI were preprocedure systolic blood pressure (odds ratio [OR] = 0.98; 95% CI: 0.96-0.99) and absolute NC area (OR = 2.47 (95% CI: 1.14-5.36). A cutoff value of absolute NC area at ≥1.1 mm2 may serve as a significant risk predictor for no-reflow after SVG-PCI. Factors associated with MACEs and the slow/no-reflow phenomenon following PCI of the SVG can be used in risk assessment of SVG.

Hepatitis B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3.

The gene for hepatitis B virus X protein (HBx) comprises the smallest open reading frame in the HBV genome, and the protein product can activate various cell signaling pathways and regulate apoptosis, among other effects. However, in different cell types and under different external conditions, its mechanism of action differs. In the present study, the effect of HBx on the viability and apoptosis of mouse podocyte clone 5 (MPC5) cells was investigated. The cells were transfected with the HBx gene using pEX plasmid, and real-time quantitative PCR and western blot analysis were used to test the transfection efficiency and assess related protein expression. The highest expression of HBx occurred at 48 h after MPC5 cells were transfected with HBx. The expression of nephrin protein in the HBx transfection group was lower than that in blank and negative control groups. Following transfection of the HBx gene, podocyte viability was suppressed, while the rate of cell apoptosis was increased; moreover, the expression of signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 was increased compared with in the control groups. The present study suggests that STAT3 activation may be involved in the pathogenic mechanism of renal injuries caused by HBV injection. Thus STAT3 is a potential molecular target in the treatment of HBV-GN.

Drug-eluting versus bare metal stent in treatment of patients with saphenous vein graft disease: A meta-analysis of randomized controlled trials.

Drug-eluting stent (DES) and bare metal stent (BMS) are effective treatments for preventing vascular disease, but whether using DES is associated with positive clinical outcomes compared with BMS in patients with saphenous vein graft disease (SVGD) has not been established. Three electronic databases including PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were searched to identify potentially includible studies. We did a random-effects meta-analysis of randomized controlled trials (RCTs) to obtain summary effect estimates for the clinical outcomes with the use of relative risk calculated from the raw data of individual trial. Among 812 patients from 4 RCTs, DES was associated with lower risk of short-term major cardiovascular events (MACEs) when compared with BMS, whereas no significant effect on the risk of long-term MACEs. Furthermore, there was no significant difference between DES and BMS for short-term myocardial infarction (MI) and long-term MI. Similarly, DES was not associated with risk of short- and long-term mortality risk as compared with BMS. In addition, DES has no significant effect on the risk of cardiac death and stent thrombosis. Finally, DES therapy significantly reduced the risk of TLR, TVF, and TVR. SVGD patients received DES can minimize the risk of short-term MACEs, TLR, TVF, and TVR when compared with BMS. However, it does not effect on the incidence of long-term MACEs, MI, mortality, cardiac death, and stent thrombosis.

Association between mobilization of circulating endothelial progenitor cells and time or degree of injury from angioplasty in patients with exertional angina: A prospective study.

The aim of the present study was to investigate the effect of coronary artery angioplasty on the recruitment of circulating endothelial progenitor cells (EPCs) in patients with angina pectoris. A total of 66 patients treated by coronary stenting were enrolled in the PCI group and 17 patients that underwent angiography alone were enrolled in the control group. The EPC count in the blood was measured by flow cytometry prior to and at 1, 3, 5, 7 and 24 h following angioplasty in the percutaneous coronary intervention (PCI) group, and at three time-points following angiography in the control group. Differences between the two groups included the characteristics of the coronary artery lesions, the incidence of diabetes and family history of coronary heart disease. The mean surface area of the stent deployed was 335.59±234.99 mm2. No significant change in EPC count was measured in the control group. In the PCI group, a moderate and delayed increase in the number of cluster of differentiation (CD)34+/kinase domain receptor (KDR)+ EPCs occurred at 24 h post-balloon inflation compared with the baseline level. The CD133-/CD34+/KDR+ subpopulations showed undulating changes at 3, 7 and 24 h post-PCI (P=0.016, P=0.01 and P=0.032, respectively). An arch shape was displayed in CD133+/KDR+ cells; initially, a reduction occurred at 3 h and was maintained constantly until 7 h (P=0.003, P=0.013 and P=0.033 at 3, 5 and 7 h, respectively), after which a slight increase to the baseline level occurred at 24 h (P=0.084). The CD133+/CD34+ cells increased in stepwise manner until 24 h. The CD34+/KDR+ EPC change magnitude correlated significantly with a global damage index by partial correlation analysis (P<0.001). The results suggested that a time-dependent mobilization of EPCs may be initiated by PCI; the change magnitude of the CD34+/KDR+ cells was associated particularly with endothelial injury degree from the PCI procedure.

Percutaneous coronary intervention strategies and prognosis for graft lesions following coronary artery bypass grafting.

The purpose of this study was to compare the prognosis of graft-percutaneous coronary intervention (PCI) and native vessel (NV)-PCI, drug-eluting stents (DESs) and bare-metal stents (BMSs) for the treatment of graft lesions following coronary artery bypass grafting (CABG), and to determine the risk factors for major adverse cardiac events (MACEs). A total of 289 patients who underwent PCI following CABG between August 2005 and March 2010 were retrospectively analyzed. The effects on survival were compared among patients who underwent NV- and graft-PCI, and DES and BMS implantation. Additionally, the risk factors for MACEs following PCI for graft lesions were analyzed. The findings showed that MACE-free and revascularization-free survival rates were significantly higher in the NV-PCI group compared with those in the graft-PCI group. There were 63 cases (29.0%) of MACEs in the DES group and 25 cases (52.1%) in the BMS group. In patients undergoing NV-PCI, the DES group had significantly fewer MACEs and less target vessel revascularization (TVR) than the BMS group. In patients undergoing graft-PCI, the DES group showed a tendency for fewer MACEs and a lower incidence of cardiac mortality, myocardial infarction and TVR compared with the BMS group. Diabetes, an age of >70 years and graft-PCI were independent risk factors for MACEs in patients post-PCI. It is concluded that NV-PCI has superior long-term outcomes compared with graft-PCI, and should therefore be considered as the first-line treatment for graft disease following CABG. Despite this, graft-PCI remains a viable option. DESs are the first choice for graft-PCI due to their safety and efficacy and their association with reduced mortality and MACE rate. Diabetes, older age and graft-PCI are independent risk factors for MACEs in patients post-CABG who are undergoing revascularization.