A patient with acute myocardial infarction with acute lower extremity arterial embolization underwent amputation under general anesthesia.

INTRODUCTION: Acute peripheral and coronary artery embolism are common complications of diabetes mellitus and greatly affect the clinical outcome of patients with diabetes; however, there are few reports about the symptoms and prognosis of patients with acute myocardial infarction (AMI) and concurrent acute lower extremity arterial embolism (ALEAE). CASE PRESENTATION: A 44-year-old man with a history of 4 years of type 1 diabetes was admitted to hospital after suddenly experiencing severe pain in his right lower limb and feeling tightness in the left anterior chest area. Ultrasonography revealed distal occlusion of the right superficial femoral artery, and an electrocardiogram showed acute anterior interstitial myocardial infarction. After conservative treatment for 2 days, the patient had severe necrosis of the lower limbs and secondary injury of multiple organs. Haemodialysis and heparin anticoagulant therapy were performed before amputation. Twelve days after the operation, the patient's condition was stable, and he was transferred out of the intensive care unit. CONCLUSIONS: If patients with ALEAE miss the opportunity for early treatment, even with AMI, emergency amputation under general anaesthesia is the right strategy to save lives.

Impact of continuous pharmaceutical care led by clinical pharmacists during transitions of care on medication adherence and clinical outcomes for patients with coronary heart disease: a prospective cohort study.

Objectives: The study aimed to explore the impact of a continuous pharmaceutical care (CPC) program during care transitions on medication adherence and clinical outcomes for patients with coronary heart disease (CHD). Methods: A prospective cohort study was conducted from April 2020 to February 2021. Patients diagnosed with CHD were selected and divided into intervention (CPC) and usual care (UC) groups by nurses at equal intervals based on admission time. The intervention group received CPC services provided by clinical pharmacists (including medication reconciliation, disease education, medication guidance, lifestyle counseling, and follow-up services) and usual care. The UC group received only routine medical care. The study compared medication adherence, clinical indicators (low-density lipoprotein cholesterol [LDL-C], blood pressure [BP], glycated hemoglobin [HbA1c] control rates), the incidence of adverse drug reactions (ADRs), and readmission rates (overall, major adverse cardiovascular events [MACEs]-related, and CHD risk factors-related) at admission and 1, 3, and 6 months after discharge between the two groups. Results: A total of 228 patients with CHD completed the study, including 113 patients in the CPC group and 115 patients in the UC group. There were no significant differences (p > 0.05) in both groups in demographic and clinical characteristics at baseline. A total of 101 drug-related problems were identified in the CPC group (an average of 0.89 per person). The CPC group showed significantly higher medication adherence at 1, 3, and 6 months after discharge than the UC group (p < 0.05). At 3 and 6 months after discharge, the intervention group had significantly higher control rates of LDL-C (61.11% vs. 44.64% at 3 months, 78.18% vs. 51.43% at 6 months), and BP (91.15% vs. 77.39% at 3 months, 88.50% vs. 77.19% at 6 months). The CPC group had higher HbA1c control rates (53.85% vs. 34.21% at 3 months, 54.05% vs. 38.46% at 6 months) than the UC group. However, the differences were not statistically significant. The incidence of ADRs 6 months after discharge was significantly lower in the CPC group than in the UC group (5.13% vs. 12.17%, p < 0.05). The CPC group had a lower overall readmission rate (13.27% vs. 20.00%), MACE-related readmission rate (5.31% vs. 12.17%), and readmission rate related to CHD risk factors (0.88% vs. 2.61%) 6 months after discharge compared to the UC group. However, these differences were not statistically significant (p > 0.05). Conclusion: CPC led by clinical pharmacists during care transitions effectively improved medication adherence, safety, and risk factor control in patients with CHD.

Effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression and oxidative stress response in rats with myocardial ischemia-reperfusion.

This study aimed to investigate the effects of miR-145-5p on cardiomyocyte proliferation and apoptosis, GIGYF1 expression, inflammation, and oxidative stress in rats with myocardial ischemia-reperfusion injury (IRI). For this purpose, SPF male SD rats were used for IRI modeling. Experimental animals were subjected to specimen sampling and myocardial HE staining. The relative expression of miR-145-5p was detected by qRT-PCR; the protein expressions of GIGYF1, p-AKT, p53, Bax, p38MAPK, and ERK1/2 were detected by Western blot. Mouse embryonic cardiomyocytes H9C2 were used for H/R modeling, which was then subjected to cell transfection according to different grouping protocols. The target of miR-145-5p was confirmed to be GIGYF1 by dual-luciferase reporter assay. Further experiments were performed to detect the survival rate of transfected cells, the apoptosis of transfected cells, SOD activity determination, as well as IL-1ß and IL-6 concentrations. The results showed that the expression level of miR-145-5p was downregulated in H2C2 cells (P < 0.05). After 24h of transfection, there was a significant increase in the expression of miR-145-5p in the H/R+miR-145-5p mimic group (P < 0.05), but an evident decrease in the H/R+miR-145-5p inhibitor group (P > 0.05). Compared with the H/R+NC inhibitor group, the H/R+miR-145-5p mimic group had significantly increased cell proliferation, improved release of SOD, and upregulated expressions of ERK1/2 and p-AKT; but downregulated concentrations of IL-1ß and IL-6, and decreased expressions of P38MAPK, p53, and Bax (all P < 0.05). Also, the IRI+miR-145-5p agomir group had significantly upregulated expression of miR-145-5p and improved injury degree of heart tissue improved; a significant increase in the protein expressions ERK1/2 and p-AKT, but downregulated protein expressions of P38MAPK, p53, and Bax (all P < 0.05). Dual-luciferase reporter assay identified that GIGYF1 was the target gene of miR-145-5p. Furthermore, through the stimulated overexpression of miR-145-5p, there were significantly increased cell proliferation, improved release of SOD, and upregulated expressions of ERK1/2 and p-AKT; but downregulated concentrations of IL-1ß and IL-6, and decreased expressions of P38MAPK, p53, and Bax (all P < 0.05), while the above trends were reversed following the simultaneous upregulation of miR-145-5p and GIGYF1 (all P < 0.05). In general, our study confirmed a decreased expression of miR-145-5p and increased expression of GIGYF1 in the IRI or H/R model in vivo and in vitro. Overexpression of miR-145-5p can downregulate the expression of GIGYF1, further promote cell proliferation, inhibit cell apoptosis, alleviate inflammation and oxidative stress, and hence exert a protective role in myocardial infarction IRI.

Left Atrial Enlargement and the Risk of Stroke: A Meta-Analysis of Prospective Cohort Studies.

Background: The association between left atrial size and the risk of stroke has not been fully understood. We performed a meta-analysis of prospective cohort studies to determine whether left atrial enlargement (LAE) is associated with an increased risk of stroke. Methods: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library through May 2019. Prospective cohort studies were included if they reported hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of stroke with respect to LAE. All meta-analyses were performed using a random-effects model. Results: Six studies involving 66,007 participants and 3,549 stroke events were included. Compared with patients without LAE, those with LAE had an increased risk of stroke (adjusted HR 1.68, 95% CI 1.36-2.07). There was also a graded association with stroke relating to LAE (adjusted HR for mild LAE 1.50, 95% CI 0.98-2.28; moderate LAE 1.40, 95% CI 1.12-1.75; and severe LAE 1.59, 95% CI 1.33-1.90). Furthermore, for each increase of 1 cm in left atrial diameter, the odds of stroke were increased by 24% (adjusted HR 1.24, 95% CI 1.03-1.50). Conclusions: Our meta-analysis demonstrated that LAE is associated with an increased and graded risk of stroke.

The protein elicitor Hrip1 enhances resistance to insects and early bolting and flowering in Arabidopsis thaliana.

The elicitor Hrip1 isolated from necrotrophic fungus Alternaria tenuissima, could induce systemic acquired resistance in tobacco to enhance resistance to tobacco mosaic virus. In the present study, we found that the transgenic lines of Hrip1-overexpression in wild type (WT) Arabidopsis thaliana were more resistant to Spodoptera exigua and were early bolting and flowering than the WT. A profiling of transcription assay using digital gene expression profiling was used for transgenic and WT Arabidopsis thaliana. Differentially expressed genes including 40 upregulated and three downregulated genes were identified. In transgenic lines of Hrip1-overexpression, three genes related to jasmonate (JA) biosynthesis were significantly upregulated, and the JA level was found to be higher than WT. Two GDSL family members (GLIP1 and GLIP4) and pathogen-related gene, which participated in pathogen defense action, were upregulated in the transgenic line of Hrip1-overexpression. Thus, Hrip1 is involved in affecting the flower bolting time and regulating endogenous JA biosynthesis and regulatory network to enhance resistance to insect.

Prognostic Value of Plasma Intermedin Level in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

Intermedin (IMD), an autocrine/paracrine biologically active peptide, plays a critical role in maintaining vascular homeostasis. Recent research has shown that high plasma levels of IMD are associated with poor outcomes for patients with ST-segment elevation acute myocardial infarction. However, the prognostic utility of IMD levels in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has not yet been investigated. We hypothesized that the level of plasma IMD would have prognostic value in patients with NSTE-ACS. Plasma IMD was determined by radioimmunoassay in 132 NSTE-ACS patients on admission to hospital and 132 sex- and age-matched healthy-control subjects. Major adverse cardiovascular events (MACEs), including death, heart failure, hospitalization, and acute myocardial infarction, were noted during follow-up. In total, 23 patients suffered MACEs during the follow-up period (mean 227 ±â€Š118 days, range 2-421 days). Median IMD levels were higher in NSTE-ACS patients than control [320.0 (250.9/384.6) vs. 227.2 (179.7/286.9) pg/mL, P <0.001]. The area under the receiver-operating characteristic curve for IMD and N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) did not significantly differ (0.73 and 0.79, both P <0.001, respectively; P = 0.946). ROC curve analysis revealed a cut-off value for IMD at 340.7 pg/mL. Cox regression analysis with cardiovascular risk variables and NT-proBNP showed that the risk of MACEs increased by a factor of 12.96 (95% CI, 3.26-49.42; P <0.001) with high IMD levels (at the cut-off value). IMD has potential as a prognostic biomarker for predicting MACEs in patients with NSTE-ACS.

Reciprocal interaction between macrophages and T cells stimulates IFN-γ and MCP-1 production in Ang II-induced cardiac inflammation and fibrosis.

BACKGROUND: The inflammatory response plays a critical role in hypertension-induced cardiac remodeling. We aimed to study how interaction among inflammatory cells causes inflammatory responses in the process of hypertensive cardiac fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: Infusion of angiotensin II (Ang II, 1500 ng/kg/min) in mice rapidly induced the expression of interferon γ (IFN-γ) and leukocytes infiltration into the heart. To determine the role of IFN-γ on cardiac inflammation and remodeling, both wild-type (WT) and IFN-γ-knockout (KO) mice were infused Ang II for 7 days, and were found an equal blood pressure increase. However, knockout of IFN-γ prevented Ang II-induced: 1) infiltration of macrophages and T cells into cardiac tissue; 2) expression of tumor necrosis factor α and monocyte chemoattractant protein 1 (MCP-1), and 3) cardiac fibrosis, including the expression of α-smooth muscle actin and collagen I (all p<0.05). Cultured T cells or macrophages alone expressed very low level of IFN-γ, however, co-culture of T cells and macrophages increased IFN-γ expression by 19.8±0.95 folds (vs. WT macrophage, p<0.001) and 20.9 ± 2.09 folds (vs. WT T cells, p<0.001). In vitro co-culture studies using T cells and macrophages from WT or IFN-γ KO mice demonstrated that T cells were primary source for IFN-γ production. Co-culture of WT macrophages with WT T cells, but not with IFN-γ-knockout T cells, increased IFN-γ production (p<0.01). Moreover, IFN-γ produced by T cells amplified MCP-1 expression in macrophages and stimulated macrophage migration. CONCLUSIONS/SIGNIFICANCE: Reciprocal interaction between macrophages and T cells in heart stimulates IFN-γ expression, leading to increased MCP-1 expression in macrophages, which results a forward-feed recruitment of macrophages, thus contributing to Ang II-induced cardiac inflammation and fibrosis.

Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF ß/Smad activation and cardiac fibrosis induced by angiotensin II.

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL-6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of α-smooth muscle actin (α-SMA), transforming growth factor ß1 (TGF-ß1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of α-SMA and collagen I in fibroblasts. Moreover, TGF-ß1 expression and phosphorylation of TGF-ß downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-ß1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-ß1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis.

Interleukin-12p35 deletion promotes CD4 T-cell-dependent macrophage differentiation and enhances angiotensin II-Induced cardiac fibrosis.

OBJECTIVE: Interleukin-12 is essential for the differentiation of naïve T cells into interferon-γ-producing T cells, which regulate inflammatory responses. We investigated this process of regulating hypertension-induced cardiac fibrosis. METHODS AND RESULTS: Mice infused with angiotensin II showed a marked increase in interleukin-12p35 expression in cardiac macrophages. The degree of cardiac fibrosis was significantly enhanced in interleukin-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to angiotensin II. Fibrotic hearts of p35-KO mice showed increased accumulation of alternatively activated (M2) macrophages and expression of M2 genes such as Arg-1 and Fizz1. Bone marrow-derived macrophages from WT or p35-KO mice did not differ in differentiation in response to angiotensin II treatment; however, in the presence of CD4(+) T cells, macrophages from p35-KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factor-ß. Moreover, CD4(+) T-cell-treated p35-KO macrophages could stimulate cardiac fibroblasts to differentiate into α-smooth muscle actin-positive and collagen I-positive myofibroblasts in 3-dimensional nanofiber gels. Neutralizing antibodies against transforming growth factor-ß inhibited myofibroblast formation induced by M2 macrophages. CONCLUSIONS: Deficiency in interleukin-12p35 regulates angiotensin II-induced cardiac fibrosis by promoting CD4(+) T-cell-dependent differentiation of M2 macrophages and production of transforming growth factor-ß.

Serum-glucocorticoid regulated kinase 1 regulates alternatively activated macrophage polarization contributing to angiotensin II-induced inflammation and cardiac fibrosis.

OBJECTIVE: Inflammatory responses play a pivotal role in the pathogenesis of hypertensive cardiac remodeling. Macrophage recruitment and polarization contribute to the development of cardiac fibrosis. Although serum-glucocorticoid regulated kinase 1 (SGK1) is a key mediator of fibrosis, its role in regulating macrophage function leading to cardiac fibrosis has not been investigated. We aimed to determine the mechanism by which SGK1 regulates the cardiac inflammatory process, thus contributing to hypertensive cardiac fibrosis. METHODS AND RESULTS: After angiotensin II infusion in mice, cardiac hypertrophy and fibrosis developed in wild-type but not SGK1 knockout mice, with equal levels of hypertension in both groups. Compared with wild-type hearts, SGK1 knockout hearts showed less infiltration of leukocytes and macrophages. Importantly, SGK1 deficiency led to decreased proportion of alternatively activated (M2) macrophages and increased levels of profibrotic cytokines. Angiotensin II infusion induced phosphorylation and nuclear localization of signal transducer and activator of transcription 3 (STAT3) whereas SGK1 knockout hearts showed this effect attenuated. In a 3-dimensional peptide gel culture, inhibition of STAT3 suppressed differentiation into M2 macrophages. Coculture of macrophages with cardiac fibroblasts in 3-dimensional peptide gel stimulated the expression of α-smooth muscle actin and collagen in cardiac fibroblasts. However, SGK1 knockout mice with macrophage deficiency showed reduced fibroblast-to-myofibroblast transition. CONCLUSIONS: SGK1 may play an important role in macrophage recruitment and M2 macrophage activation by activating the STAT3 pathway, which leads to angiotensin II-induced cardiac fibrosis.

Evaluation of medical treatment for peripheral arterial disease in Chinese high-risk patients.

BACKGROUND: Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is associated with elevated cardiovascular morbidity and mortality. The aim of the present study was to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme inhibitors (ACEI) in Chinese high-risk cardiovascular (CV) patients with PAD, with an emphasis on the need for aggressive medical management of all atherosclerotic manifestations. METHODS AND RESULTS: Medical records from 5,263 Chinese patients at high risk of CV were evaluated for the use of antiplatelet agents, statins and ACEI in patients with and without PAD. PAD was defined as an ankle-brachial index (ABI)<0.9 in either leg. Multivariable logistic regression analyses were performed to compare medication use in the 2 groups. A total of 5,254 patients were analyzed (52.9% male, mean age 67.3 years). The prevalence of PAD in the total patient group was 25.4%; 22.5% of them had PAD only. Overall, 5.7% had PAD only, 19.6% had PAD and coronary heart disease (CHD) or stroke or diabetes, 7.7% had CHD only, 12.6% had stroke only, and 13.6% had diabetes only. The 28.9% subjects having none of PAD, CHD, stroke or diabetes were used as the reference group. Only 65%, 37% and 47% of all patients received antiplatelet agents, statins and ACEI, respectively. Antiplatelets, statins, ACEI and all 3 medications were used less frequently in PAD only patients (58.1%, 35.9, 53.5% and 21.6%) vs CHD only (90.9%, 74.5%, 70.6% and 55.9%, p<0.001). All 3 proven efficacious therapies were prescribed for only 56% of patients with CHD only, 8% with stroke only, 13% with diabetes only and 21% with PAD only. CONCLUSION: PAD is prevalent in Chinese high-risk CV patients, equivalent to CHD, but these patients receive less intensive treatment than those with CHD. Programs to improve CV risk reduction in these high-risk patients are needed.