[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Conversion therapy in liver transplantation for hepatocellular carcinoma: What's new in the era of molecular and immune therapy?

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, with limited therapies and unsatisfactory prognosis once in the advanced stages. With promising advances in locoregional and systematic treatments, fast development of targeted drugs, the success of immunotherapy, as well as the emergence of the therapeutic alliance, conversion therapy has recently become more well developed and an effective therapeutic strategy. This article aimed to review recent developments in conversion therapy in liver transplantation (LT) for HCC. DATA SOURCES: We searched for relevant publications on PubMed before September 2022, using the terms "HCC", "liver transplantation", "downstaging", "bridging treatment" and "conversion therapy." RESULTS: Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT. Although combining various local and systematic treatments in conversion therapy is still controversial, growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time, which ultimately increases the opportunities for LT. Moreover, the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors. CONCLUSIONS: In the era of targeted therapy and immunotherapy, applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients. With the expansion of conversion therapy concepts, further investigation and research is required to realize the full potential of conversion treatment strategies, including accurately selecting candidates, determining the timing of surgery, improving the conversion rate, and guaranteeing the safety and long-term efficacy of treatment.

[Correlation between Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling Pathway and Non-infectious Diseases].

As a DNA receptor in the cytoplasm,cyclic GMP-AMP synthase (cGAS) can recognize abnormal DNA in the cytoplasm and activate stimulator of interferon genes (STING) to regulate the immune response. The recent studies have demonstrated that this pathway plays a role in non-infectious inflammatory diseases by promoting the expression of type Ⅰ interferon and interferon-stimulated gene.This article reviews the activation and regulation of cGAS-STING pathway in multiple systems and the effect of this pathway on the occurrence and progression of non-infectious inflammatory diseases,providing theoretical reference for future application of cGAS-STING pathway-related drugs in non-infectious inflammatory diseases.

Aldehyde dehydrogenase 2 Glu504Lys variant predicts a worse prognosis of acute coronary syndrome patients.

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys variant was an independent risk factor for acute coronary syndrome (ACS). However, there are lacking researches about the relationship between the variant and prognosis of ACS. In the prospective study, 377 ACS patients were grouped into the wild-type (*1/*1) and the mutation (*2/*2 + *1/*2) groups according to genotype detection. Compared with the wild-type group, incidences of major adverse cardiac events (MACE) and cardiac death were both higher in the mutation group (9.2% vs 21.0%, P = .002; 5.2% vs 12.2%, P = .026); the MACE-free and the cardiac-death-free cumulative survival rates were obviously lower in the mutation group. Moreover, the mutant genotypes were associated with significantly increased risk of MACE and cardiac death (HR 2.443, 95%CI: 1.390-4.296, P = .002; HR 2.727, 95%CI: 1.303-5.708, P = .008). These results suggested that ALDH2 Glu504Lys variant could predict a worse prognosis of ACS patients.

Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.

Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 µg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM.

Chemotactic dynamics of catalytic dimer nanomotors.

Synthetic chemically powered nanomotors possessing the ability of chemotaxis are desirable for target cargo delivery and self-assembly. The chemotactic properties of a sphere dimer motor, composed of linked catalytic and inactive monomers, are studied in a gradient field of fuel. Particle-based simulation is carried out by means of hybrid molecular dynamics/multiparticle collision dynamics. The detailed tracking and motion analysis describing the running and tumbling of the sphere dimer motor in the process of chemotaxis are investigated. Physical factors affecting chemotactic velocity are discussed, and quantitative relations are presented. The influence of the geometry of sphere dimer motors on the chemotactic dynamics is explored, which is beneficial for the design of motors with high sensitivity for detecting the surrounding environment.

Aldehyde dehydrogenase 2 polymorphism as a protective factor for intracranial vascular stenosis in ischemic stroke in Han Chinese.

AIM: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that metabolizes acetaldehyde to acetic acid. ALDH2 gene polymorphism modifies its activity and the mutation of ALDH2 gene has been reported to be associated with the protection against ischemic stroke. However, the potential association of allelic variation of ALDH2 with intracranial vascular stenosis and the clinical characteristics of ischemic stroke without coronary artery disease remains unclear. METHODS: In this study, ischemic stroke patients were recruited, National Institutes of Health Stroke Scale scores were analyzed, intracranial arterial stenosis were evaluated by magnetic resonance angiography and gene typing of ALDH2 was determined by polymerase chain reaction and sequencing. RESULTS: We found that the rate of heavy drinking was significantly lower in the ALDH2 mutation group ((*)1/(*)2 and (*)2/(*)2) than in wild-type group ((*)1/(*)1) (18.6% vs. 38.0%, p = 0.01). Plasma homocysteine (Hcy) levels were significantly different in the two groups (15.45 ± 6.39 vs. 13.14 ± 4.45, p = 0.015). The ALDH2 mutation genotype was negatively correlated with severe intracranial vascular stenosis (OR, 0.34; p = 0.002), even after adjustment for high-density lipoprotein cholesterol, Hcy, and heavy drinking (adjusted OR, 0.44; p = 0.03). CONCLUSION: ALDH2(*)2 could be a protective factor and negative predictor for severe intracranial vascular stenosis in ischemic stroke in Han Chinese.

Angiotensin-(1-7) treatment mitigates right ventricular fibrosis as a distinctive feature of diabetic cardiomyopathy.

In diabetic patients, left ventricular (LV) remodeling is highly prevalent; however, little is known about the impact of diabetes on right ventricular (RV) structure and function. We recently found that overexpression of angiotensin (ANG)-converting enzyme 2 (ACE2), which metabolizes ANG-II to ANG-(1-7) and ANG-I to ANG-(1-9), may improve LV remodeling in diabetic cardiomyopathy (DCM). Here, we aimed to assess whether LV remodeling and dysfunction are paralleled by RV alterations and the effects of ANG-(1-7) on RV remodeling in DCM. After 12 wk of diabetes induced by a single intraperitoneal injection of streptozotocin, rats were treated with saline, ANG-(1-7), perindopril, ANG-(1-7) plus perindopril, ANG-(1-7) plus Mas receptor antagonist A779, or ANG-(1-7) plus ANG-II type 2 receptor antagonist PD123319 for 4 wk. RV remodeling in diabetic rats was indicated by fibrosis of the RV free wall in the absence of hypertrophy and apoptosis. Treatment with ANG-(1-7) prevented diabetes-induced RV fibrosis and dysfunction. ANG-(1-7) (800 ng·kg(-1)·min(-1)) was superior to perindopril in improving RV fibrosis. The major mechanisms involved a complex interaction of ANG-II type 2 and Mas receptors for subsequent downregulation of ACE expression and activity and ANG-II type 1 receptor expression, as well as upregulation of ACE2 expression and activity and the expression of ANG-II type 2 receptor and sarco(endo)plasmic reticulum Ca(2+)-ATPase. Thus RV fibrosis and dysfunction plays a central role in DCM, and ANG-(1-7) mitigates diabetes-induced RV alterations.

Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: from bench to bedside.

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.

Poly(ADP-ribose) polymerase inhibition prevents reactive oxygen species induced inhibition of aldehyde dehydrogenase2 activity.

Lipid peroxidation plays a critical role in cardiovascular diseases. Aldehydes are the major end products of lipid peroxidation and can be metabolized into less reactive chemical species by aldehyde dehydrogenase 2 (ALDH2). However, ALDH2 dehydrogenase activity can be affected by many factors including reactive oxygen species. To elucidate how reactive oxygen species inhibit ALDH2 dehydrogenase activity, we stimulated human aortic endothelial cells (HAECs) with oxidized low-density lipoproteins (ox-LDL) and performed a myocardial ischemia-reperfusion model. Ox-LDL treatment and ischemia-reperfusion injury inhibited ALDH2 dehydrogenase activity. Poly(ADP-ribose) polymerase (PARP) was activated by ox-LDL stimulation and ischemia-reperfusion injury and PARP inhibition partly restored ALDH2 dehydrogenase activity in ox-LDL treated HAECs and ischemia-reperfusion rat hearts. SIRT3 was upregulated by ox-LDL stimulation and ischemia-reperfusion injury and downregulated by PARP inhibition. Using siRNA to knock down SIRT3, we demonstrated that SIRT3 mediated deacetylation decreased ALDH2 dehydrogenase activity and PARP inhibition partly restored ALDH2 dehydrogenase activity through preventing SIRT3 expression and subsequently preserving ALDH2 acetylation.

Circulating CD36 and fractalkine levels are associated with vulnerable plaque progression in patients with unstable angina pectoris.

The chemokine, fractalkine, independently enhances the vulnerability of coronary atherosclerotic plaques. The present study investigated the combined effects of CD36 and fractalkine on coronary plaque progression in patients with unstable angina pectoris. In the present study, 120 unstable angina pectoris patients undergoing coronary angiography and intravascular ultrasound were divided into two groups: an intermediate lesion group (lumen diameter stenosis 50-70%, 80 patients) and a severe lesion group (at least one lesion with lumen diameter stenosis > 70%, 40 patients). The control group consisted of 40 healthy age- and sex-matched subjects. Concentrations of CD36 and fractalkine were measured by enzyme-linked immunosorbent assay. Major adverse cardiovascular events were monitored over a 2-year follow up. Intravascular ultrasound showed that patients with severe lesions had more calcified and mixed plaques, and a larger plaque area and plaque burden than patients with intermediate lesions (P < 0.05-0.01). More patients with severe lesions underwent stent deployment (P < 0.05) than those with intermediate lesions. CD36 and fractalkine concentrations were significantly higher in the severe lesion patients (P < 0.05), and both had significant positive correlations (P < 0.05) with the plaque burden of atherosclerotic lesions. Using the matched nested case-control study, we found that CD36 and fractalkine levels were higher in patients with recurrent major adverse cardiovascular events than controls (P < 0.05). In conclusion, CD36 and fractalkine both promote, and might synergistically enhance, the progression of coronary atherosclerotic plaques.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice.

Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

Tetramethylpyrazine upregulates the aquaporin 8 expression of hepatocellular mitochondria in septic rats.

BACKGROUND: The sepsis-induced acute liver injury majorly depends on the dysfunction of mitochondria and the loss of cellular energy. Aquaporin 8 (AQP8) can modulate water transport and osmotic swelling of mitochondria in the inner mitochondrial membrane of the liver. In this study, we explore the effects of tetramethylpyrazine (TMP) on protecting the structure of hepatocyte mitochondria and modulating the expression of AQP8. MATERIALS AND METHODS: Forty-eight rats were randomly allocated to four groups: control group receiving sham procedure, septic group receiving cecal ligation and puncture (CLP), therapeutic group receiving 60 mg/kg of ligustrazine (TMP) intravenously from caudal vein immediately after CLP, and preventive group receiving 60 mg/kg/d of ligustrazine intravenously from caudal vein for 7 d before CLP. The mitochondrial ultrastructure of rat liver was observed. The protein expression of AQP8 was assayed by Western blot. Analysis of AQP8 messenger RNA (mRNA) expression level was performed by the reverse transcription-polymerase chain reaction. The mean fluorescence intensity (MFI) of rhodamine 123 (Rh 123) was measured by flow cytometry. The serum tumor necrosis factor alpha (TNF-α) level was determined by the enzyme-linked immunosorbent assay. RESULTS: The mitochondrial ultrastructure was markedly damaged in the septic group, whereas it was lightly damaged in the therapeutic and preventive groups. Compared with the control group, the AQP8 protein expression and MFI were significantly reduced, and the steady-state AQP8 mRNA and serum TNF-α levels were increased in the septic, therapeutic, and preventive groups. Compared with the septic group, the AQP8 protein expression and MFI were increased, and the steady-state AQP8 mRNA and serum TNF-α levels were decreased significantly in the therapeutic and preventive groups. There was no significant difference in morphologic characteristics, AQP8 protein level, AQP8 mRNA level, MFI, and serum TNF-α level between the therapeutic and the preventive groups. Linear positive correlation was observed between the AQP8 protein level and the MFI of Rh 123. Linear negative correlation was observed between the AQP8 protein level or the MFI of Rh 123 and serum TNF-α level. CONCLUSIONS: TMP has protective effect on hepatocellular mitochondria from damage in sepsis by ameliorating the expression of AQP8 protein in liver mitochondria. The protective effect of TMP on the liver mitochondria might not have a difference between using TMP before or after the occurrence of sepsis.

Alpha-lipoic acid ameliorates oxidative stress by increasing aldehyde dehydrogenase-2 activity in patients with acute coronary syndrome.

Aldehyde dehydrogenase-2 (ALDH2) is the main enzyme responsible for acetaldehyde oxidation in ethanol metabolism and also provides protection against oxidative stress. Alpha-lipoic acid (α-LA), a natural dithiol compound with antioxidant properties, has been reported to increase ALDH2 activity in cultured cells. We analyzed the therapeutic efficacy of α-LA in 63 patients with confirmed acute coronary syndrome (ACS). These patients (52 men and 11 women, with age range 49-72 years) were randomized into two groups: untreated group (n = 30) and α-LA group (n = 33). Patients in the α-LA group were given an intravenous injection of 600 mg α-LA every day for 5 days while the patients in the untreated group were given saline. An isoprostane, 8-iso-prostaglandin F2α (8-iso-PGF2α), one product of arachidonic acid metabolism, was measured as a marker for oxidative stress. The serum levels of 8-iso-PGF2α and ALDH2 activity were determined at admission to the hospital (time 0), and at 24 hours and 1 week after treatment. At 24 hours and 1 week after treatment, ALDH2 activity was significantly higher in the α-LA group than in the untreated group (P < 0.05), whereas the levels of 8-iso-PGF2α were significantly lower in the α-LA group than in the untreated group (all P < 0.05). Importantly, the decrease of 8-iso-PGF2α levels correlated with the increased ALDH2 activity at both 24 hours (r = 0.6234, P < 0.001) and 1 week after treatment (r = -0.3941, P = 0.0014). α-LA may ameliorate oxidative stress through up-regulating ALDH2 activity in patients with ACS.

Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus.

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.

Arginase I attenuates inflammatory cytokine secretion induced by lipopolysaccharide in vascular smooth muscle cells.

OBJECTIVE: Inflammation plays an important role in atherosclerosis. Arginase I (Arg I) promotes the proliferation of vascular smooth muscle cells; however, the effect of Arg I on inflammation remains unknown. The present study investigated the role of Arg I in inflammation in vitro and in vivo. METHODS AND RESULTS: Quantitative reverse transcription-polymerase chain reaction and Western blot analysis demonstrated that Arg I inhibited tumor necrosis factor-α production induced by lipopolysaccharide in human aortic smooth muscle cells. Inducible nitric oxide synthase substrate competition and nuclear factor-κB activation were main contributors to lipopolysaccharide-mediated inflammatory cytokine generation. However, Arg I could attenuate the function of inducible nitric oxide synthase and inhibit the subsequent nuclear factor-κB activation, leading to inhibition of tumor necrosis factor-α generation. Furthermore, upregulation of Arg I significantly decreased macrophage infiltration and inflammation in atherosclerotic plaque of rabbits, whereas downregulation of Arg I aggravated these adverse effects. CONCLUSIONS: The results indicate the antiinflammatory effects of Arg I and suggest an unexpected beneficial role of Arg I in inflammatory disease.

Simvastatin exerts cardioprotective effects and inhibits the activity of Rho-associated protein kinase in rats with metabolic syndrome.

1. Insulin resistance (IR) is crucially involved in the pathophysiology of metabolic syndrome (MS). The aim of the present study was to investigate the effects of simvastatin on IR in rats with MS. 2. A rat model of MS was established and myocardial damage was examined by transmission electron microscopy. Twenty-two MS rats were divided into two groups of 11 rats each: (i) an MS group; and (ii) a simvastatin-treated MS. Ten Wistar rats were used as controls. The phosphorylation of myosin phosphatase target subunit 1 (MYPT-1), insulin receptor substrate 1 (IRS-1) and Akt were analysed by immunohistochemistry and western blotting. 3. Insulin resistance-induced MS was associated with a significant increase in Rho kinase (ROCK) activity and inhibition of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Decreased levels of phosphorylated (p-) MYPT-1 and p-IRS-1 (Ser³°7) and increased levels of p-Akt were found in hearts from the MS + simvastatin compared with the MS group. These results suggest that simvastatin reduces ROCK activity and increases Akt activity. 4. Simvastatin exerts cardioprotective effects and improves IR, which can be attributed, at least in part, to the inhibition of ROCK and activation of PI3-K/Akt.

The combination of creatine kinase-myocardial band isoenzyme and point-of-care cardiac troponin/ contemporary cardiac troponin for the early diagnosis of acute myocardial infarction.

BACKGROUND: The early diagnosis of acute myocardial infarction (AMI) remains challenging, especially for institutions without the high-sensitive cardiac troponin (hs-cTn) assay. Herein, we aim to assess the value of creatine kinase-myocardial band isoenzyme (CK-MB) combined with different cardiac troponin (cTn) assays in AMI diagnosis. METHODS: This multicenter, observational study included 3,706 patients with acute chest pain from September 1, 2015, to September 30, 2017. We classified the participants into three groups according to the cTn assays: the point-of-care cTn (POC-cTn) group, the contemporary cTn (c-cTn) group, and hs-cTn group. The diagnostic value was quantified using sensitivity and the area under the curve (AUC). RESULTS: Compared to the single POC-cTn/c-cTn assays, combining CK-MB and POC-cTn/c-cTn increased the diagnostic sensitivity of AMI (56.1% vs. 63.9%, P<0.001; 82.7% vs. 84.3%, P=0.025). In contrast, combining CK-MB and hs-cTn did not change the sensitivity compared with hs-cTn alone (95.0% vs. 95.0%, P>0.999). In the subgroup analysis, the sensitivity of combining CK-MB and c-cTn increased with time from symptom onset <6 h compared with c-cTn alone (72.8% vs. 75.0%, P=0.046), while the sensitivity did not increase with time from symptom onset >6 h (97.5% vs. 98.3%, P=0.317). The AUC of the combination of CK-MB and POC-cTn significantly increased compared to the single POC-cTn assay (0.776 vs. 0.750, P=0.002). The AUC of the combined CK-MB and c-cTn/hs-cTn assays did not significantly decrease compared with that of the single c-cTn/hs-cTn assays within 6 h. CONCLUSIONS: The combination of CK-MB and POC-cTn or c-cTn may be valuable for the early diagnosis of AMI, especially when hs-cTn is not available.

Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome.

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.