Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study.

BACKGROUND: In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. METHODS: Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR. RESULTS: During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04-2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23-5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1-2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05). CONCLUSION: High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.

MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated ß-galactosidase (SA-ß-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence.

New Insights into the Role of HMGB2 in ST-Segment Elevation Myocardial Infarction.

Background: Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated. Methods: We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets. Results: We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbß3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2). Conclusion: In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.

Protective Effect of Nicorandil on Contrast-Induced Acute Kidney Injury After Emergency Percutaneous Coronary Intervention.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n = 55) and the control group (n = 101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 µmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and ß2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P = .043). Compared with the control group, Scr, uric acid, and ß2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P = .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

Incidence of coronary drug-eluting stent fracture: A systematic review and meta-analysis.

Background: Reported evidence of coronary stent fracture (CSF) has increased in recent years. The purpose of this study was to determine reliable estimates of the overall incidence of CSF. Methods and results: The MEDLINE, Embase and Cochrane databases were searched until March 18, 2022. Pooled estimates were acquired using random effects models. Meta-regression and subgroup analysis were used to explore sources of heterogeneity, and publication bias was evaluated by visual assessment of funnel plots and Egger's test. Overall, 46 articles were included in this study. Estimates of CSF incidence were 5.5% [95% confidence interval (CI): 3.7-7.7%] among 39,953 patients based on 36 studies, 4.8% (95% CI: 3.1-6.8%) among 39,945 lesions based on 29 studies and 4.9% (95% CI: 2.5-9.4%) among 19,252 stents based on 8 studies. There has been an obvious increase in the incidence of CSF over the past two decades, and it seems that the duration of stent placement after stent implantation has no impact on incidence estimation. Conclusion: The incidence of CSF was 5.5% among patients, 4.8% for lesions and 4.9% for stents and increased over the past 20 years. The duration of stent placement after stent implantation was found to have no impact on the incidence of CSF, but drug-eluting stent (DES) types and right coronary artery (RCA) lesions influenced the pooled incidence. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311995], identifier [CRD42022311995].

Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis.

BACKGROUND: Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients. METHODS: In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups. RESULTS: Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE. CONCLUSION: Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.

Comparing the efficacy of angiotensin receptor-neprilysin inhibitor and enalapril in acute anterior STEMI patients after primary percutaneous coronary intervention: a prospective randomized trial.

Background: For patients with heart failure (HF), the effect of angiotensin receptor-neprilysin inhibitors (ARNIs, sacubitril/valsartan) on cardiac remodeling has been found to be superior to angiotensin-converting enzyme inhibitors (ACEI). However, little data have described the impact of early-initiation ARNI in patients with acute anterior ST-segment elevation myocardial infarction (STEMI). Methods: In this prospective, randomized, double-blind, parallel-group trial, we enrolled 131 anterior STEMI patients who were treated with primary percutaneous coronary intervention (PCI) between February 2019 and December 2019. All patients received standard STEMI management and were divided into 2 groups (ARNI/enalapril). Primary efficacy outcomes were the between-group difference in change (from baseline to 4-, 12-, and 24-week) in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration, left ventricular ejection fraction (LVEF), and left ventricular end-systolic volumes and end-diastolic volumes (LVESV and LVEDV). Secondary outcomes were determined by a composite of death, reinfarction, outpatient HF or HF hospitalization, malignant arrhythmia, and stroke. Safety outcomes included worsening renal function, hypotension, hyperkalemia, angioedema and cough. Results: We found that NT-proBNP concentration decreased more in the ARNI group than in the enalapril group [4 weeks: ratio of ARNI vs. enalapril 0.36, 95% confidence interval (CI): 0.24 to 0.52, P<0.001; 12 weeks: 0.54, 95% CI: 0.35 to 0.79, P<0.001; 24 weeks: 0.53, 95% CI: 0.32 to 0.83, P<0.001). When compared to the enalapril group, the ARNI group patients had a significant reduction in LVEDV (P<0.001) and LVESV (P<0.001), and an improvement in LVEF (P=0.011) at 24 weeks. Secondary outcomes occurred in 13 participants (20.3%) in the ARNI group and 22 participants (34.4%) in the enalapril group [hazard ratio (HR), 0.56; 95% CI: 0.28 to 1.12; P=0.102]. The incidence of outpatient HF or HF hospitalization in the ARNI group was significantly lower than that in the enalapril group (HR, 0.36; 95% CI: 0.14 to 0.94; P=0.037). There were no significant differences in the safety between the 2 groups. Conclusions: For patients with acute anterior STEMI undergoing primary PCI, early initiation of ARNI provided significant clinical benefits. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100042944) registered on February 1, 2021.

Anxiety is associated with higher blood pressure rise induced by cuff inflation.

SUBJECTS: To assess whether anxiety is associated with a higher rise of blood pressure induced by cuff inflation. METHODS: At first, intro-aortic blood pressure was continuously record before cuff inflation as baseline value in 234 patients underwent coronary angiography, then the cuff was inflated to 200 mmHg and the intro-aortic blood pressure was record again as cuff inflation blood pressure. According to anxiety score, the patients were divided into anxiety group, subanxiety group, and nonanxiety group. The difference between the baseline blood pressure and the cuff inflation blood pressure was calculated as cuff inflation-induced blood pressure elevation. When the difference ≥10 mmHg, cuff inflation-induced blood pressure elevation was diagnosed. RESULTS: The cuff inflation systolic blood pressure (134.9 ± 22.4 versus 131.6 ± 22.3 mmHg, P < 0.01) and diastolic blood pressure (80.5 ± 11.9 versus 78.4 ± 11.6 mmHg, P < 0.01) were significantly higher than the baseline values, thus the mean cuff inflation-induced blood pressure elevation on systolic blood pressure was 3.3 ± 4.7 mmHg and that on diastolic blood pressure was 2.1 ± 4.9 mmHg. The anxiety subgroup had significantly higher percentage increase-systolic blood pressure and percentage increase-diastolic blood pressure levels (4.5 ± 3.1% and 5.6 ± 6.3%) than the nonanxiety subgroup (1.9 ± 3.3% and 2.0 ± 6.5%), meanwhile these values in the subanxiety subgroup were higher (3.2 ± 4.1% and 3.4 ± 5.7%) than the nonanxiety subgroup. CONCLUSION: Cuff inflation can induce a transient rise of intro-aortic blood pressure. Anxiety is associated with higher cuff inflation-induced blood pressure elevation.

Blood microRNA 202-3p associates with the risk of essential hypertension by targeting soluble ST2.

MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P<0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36-1.82; P<0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II.

Lichen striatus versus linear lichen planus: a comparison of clinicopathological features, immunoprofile of infiltrated cells, and epidermal proliferation and differentiation.

BACKGROUND: Lichen striatus (LS) and linear lichen planus (LLP) are separate uncommon disorders belonging to linear inflammatory dermatoses. The immunotyping of inflammatory cells has been investigated in LS and lichen planus (LP), but epidermal proliferation and differentiation have little been described in LS and LLP. METHODS: The clinical and pathological data of eight patients with LS and seven with LLP were retrospectively collected. Immunotyping of infiltrated cells and expression of Ki-67, K16, involucrin, and filaggrin were stained by immunohistochemistry in skin lesions of these patients and normal skin of eight healthy controls. RESULTS: Dermal infiltrates contained primarily CD3+ and CD68+ cells in three groups. CD4+ cells were predominantly located in the perivascular area, while CD8+ cells were frequently close to the junctional zone. Compared with control skin, epidermal and dermal CD1a+ cells, and dermal CD3+, CD4+, CD8+, and CD68+ cells were increased in LS and LLP (P < 0.05), while Ki-67+ cells were significantly high in LLP (P < 0.05) but not in LS. K16 and involucrin expression in LLP were more extensive than in LS, and filaggrin expression was similar between both entities. CONCLUSIONS: Our results indicate that the predominance of CD8+ cells and increased epidermal proliferation and abnormal keratinization are present in both dermatoses, although the levels of the above indexes are mild in LS as compared to LLP. These two entities might be due to the interaction of infiltrated cells and keratinocytes, and CD8+ cells could play a pivotal role in their pathogenesis.

Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.