Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Cardiopulmonary exercise test combined with red blood cell distribution width to predict cardiovascular complication of thoracic surgery.

Cardiovascular complications in patients undergoing thoracic surgery, which physicians have a limited ability to predict, are often unavoidable and resulting in adverse outcome. Cardiopulmonary exercise testing (CPET), the gold standard of cardiopulmonary function evaluation, has also been proved to be a preoperative risk assessment tool. Meanwhile, elevated red blood cell distribution width (RDW) has surged as a biochemical marker in the occurrence of cardiovascular disease. However, it is yet unclear the value of CPET combined with RDW in predicting cardiovascular complications after thoracic surgery. 50 patients with cardiovascular complications after thoracic surgery were collected as the case group, and 100 thoracic surgery patients were recruited as the control group, with the same gender, age ± 2 years old, and no postoperative complications. After admission, all patients underwent CPET and RDW inspection before surgery, and the results were recorded. The CPET parameter oxygen pulse (VO2/HR) and RDW of the case group were lower than those of the control group (P < 0.05), and the ventilation/carbon dioxide production (VE/VCO2 slope) was significantly higher than control group (P < 0.01). The biochemical parameters hemoglobin (Hb) and Glomerular filtration rate (GFR)) of the case group were lower than those of the control group (P < 0.05), the homocysteine (hCY), creatinine (Cr), operation time and blood loss of the case group were higher than those of the control group (P < 0.05). The RDW had a negative correlation with VO2 max in both overall and control group. The combination of VO2/kg and RDW had the highest diagnostic value in predicting cardiovascular complications. The combination of VO2/kg and RDW has predictive diagnostic value and is more suitable for predicting postoperative complications of thoracic surgery.

Dynamics of The Γδtcr Repertoires During The Dedifferentiation Process and Pilot Implications for Immunotherapy of Thyroid Cancer.

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.

ΔRDW Could Predict Major Adverse Cardiovascular Events in Patients with Heart Failure with Reduced Ejection Fraction After Sacubitril/Valsartan Treatment.

Objective: This study aimed to evaluate the association between red blood cell distribution width (RDW) changes and major adverse cardiovascular event (MACE) occurrences during sacubitril/valsartan treatment in patients with heart failure with reduced ejection fraction (HFrEF). Methods: This study retrospectively analyzed the medical records of patients with HFrEF hospitalized from April 2018 to February 2021. The patients were divided into two groups according to the inclusion of sacubitril/valsartan in the personal drug treatment regimen, the traditional and the sacubitril/valsartan group. RDW values before and after sacubitril/valsartan treatment were recorded respectively as RDW1 and RDW2. ΔRDW was defined as the difference between RDW2 and RDW1. The patients in the sacubitril/valsartan group were divided into two subgroups according to ΔRDW >0 or ≤0. MACEs, such as readmission for HF, acute myocardial infarction, ischemic stroke, and malignant arrhythmia and death, were recorded during the 1-year follow-up period in each group. Results: MACE development was lower in patients treated with sacubitril/valsartan than those treated with conventional therapy (log-rank, P<0.001). The incidence of cardiac events during the follow-up period was greater in the group with ΔRDW >0 than in the group with ΔRDW ≤0 (Breslow, P<0.001). Increased RDW was associated with a higher likelihood of developing MACE than decreased RDW (odds ratio [OR] =2.055, 95% confidence interval [CI]:1.301-3.246), and the risk of developing MACE increased by 22.1% for each unit increase in RDW (OR=1.221, 95% CI:1.074-1.389). Conclusion: Sacubitril/valsartan treatment is effective in reducing the risk of MACEs in HFrEF. Additionally, RDW changes are predictors of MACEs after sacubitril/valsartan treatment.

FOXP1­induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox­LDL via MAP3K5 signaling pathway.

Atherosclerosis (AS) is a type of chronic inflammatory disease and the main pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten the health of patients. The dual specificity phosphatase 12 (DUSP12) protein is known as regulator of inflammatory diseases. Nonetheless, at present, there are only a few reports on the regulatory role of DUSP12 in AS. Human umbilical vein endothelial cells (HUVECs) were induced using oxidized low-density lipoprotein (ox-LDL). Subsequently, cell transfection experiments were performed to overexpress DUSP12 in ox-LDL-induced HUVECs. Cell Counting Kit-8, TUNEL western blotting, 2',7'-dichlorofluorescein diacetate assays, ELISA and other techniques were used to measure cell viability, apoptosis, inflammation, oxidative stress and endothelial function-related indicators. Subsequently, the relationship between DUSP12 and Forkhead box P1 (FOXP1) was predicted using the JASPAR database and verified using luciferase reporter and chromatin immunoprecipitation assays. Finally, the regulatory mechanism was investigated by simultaneously overexpressing DUSP12 and knocking down FOXP1 in ox-LDL-induced HUVECs and MAP3K5-related proteins of the DUSP12 downstream pathway were measured by western blotting. The expression of DUSP12 in ox-LDL-induced HUVECs was significantly decreased. Overexpression of DUSP12 inhibited apoptosis, inflammation and oxidative stress damage and alleviated endothelial dysfunction in ox-LDL-induced HUVECs. FOXP1 promoted the transcription of DUSP12. Moreover, FOXP1 alleviated ox-LDL-induced apoptosis, inflammation and oxidative stress damage in HUVECs by regulating the expression of DUSP12, probably acting through the MAP3K5 pathway. Collectively, the present study revealed that FOXP1-induced DUSP12 alleviated vascular endothelial cell inflammation and oxidative stress injury in ox-LDL-induced HUVECs via the MAP3K5 signaling pathway, which might shed novel insights into the targeted treatment for AS in the clinic.

New Clues to Cardiovascular Disease: Erythrocyte Lifespan.

Determination of erythrocyte lifespan is an important part of the diagnosis of hemolytic diseases. Recent studies have revealed alterations in erythrocyte lifespan among patients with various cardiovascular diseases, including atherosclerotic coronary heart disease, hypertension, and heart failure. This review summarizes the progress of research on erythrocyte lifespan in cardiovascular diseases.

Combined treatment with sacubitril/valsartan plus dapagliflozin in patients affected by heart failure with reduced ejection fraction.

Background: Data about real-world effects of combined therapy with sacubitril/valsartan plus dapagliflozin in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) has not been widely reported. In this article, the benefits of dapagliflozin and sacubitril/valsartan respect to improvements of cardiac function in patients with HFrEF would be investigated. Methods: HF patients prescribed sacubitril/valsartan between January 2020 and January 2022 in a tertiary teaching hospital were selected using the Computerized Patient Record System. Patients were divided into two groups according to whether they were taking dapagliflozin. Clinical parameters at baseline and during follow-up were retrospectively collected and analyzed. Results: Total of 136 consecutive patients were recruited for this study. 72 patients treated with sacubitril/valsartan and dapagliflozin were assigned to Group A, and another 64 patients receiving sacubitril/valsartan monotherapy were assigned to Group B. After treatment with sacubitril/valsartan plus dapagliflozin for a median follow-up period of 189 days (IQR, 180-276), significant improvements of cardiac function were achieved in Group A. Median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was significantly decreased from 2585 pg/ml (1014-3702.5) to 1260.5 pg/ml (439.8-2214.3) (P < 0.001). Mean left ventricular ejection fraction (LVEF) improved from 34.7 ± 4.6% to 39.2 ± 7.5% (P < 0.001). Mean daily dose of loop diuretics decreased from 37.1 ± 17.3 mg/day to 25.9 ± 18.5 mg/day (P < 0.001). Regarding safety, both systolic blood pressure (P = 0.002) and diastolic blood pressure (P = 0.002) significantly decreased. For patients in Group B, significant improvements in mean LVEF (P < 0.001), decreases in mean daily dose of loop diuretics (P = 0.001) and reductions in diastolic blood pressure (P = 0.023) were observed. Strikingly, both median Δ NT-proBNP (P = 0.04) and median Δ LAD (P = 0.006) in Group A were more pronounced in comparison with those seen in Group B. Conclusions: The combined use of sacubitril/valsartan and dapagliflozin was associated with improved cardiac function in patents with HFrEF, and led to greater reductions in LAD and NT-proBNP levels compared to sacubitril/valsartan monotherapy. These findings suggest that the combination therapy may offer more potent cardiovascular benefits.

Taxifolin ameliorates abdominal aortic aneurysm by preventing inflammation and apoptosis and extracellular matrix degradation via inactivating TLR4/NF-κB axis.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a serious aortic disease with high mortality. Vascular smooth muscle cells (VSMCs) loss is a prominent feature of AAA. Taxifolin (TXL) is a natural antioxidant polyphenol and possesses therapeutic functions in numerous human diseases. This study aimed to investigate TXL's impact on VSMC phenotype in AAA. METHODS: In vitro and in vivo of VSMC injury model was induced by angiotensin II (Ang II). The potential function of TXL on AAA was determined using Cell Counting Kit-8, flow cytometry, Western blot, quantitative reverse transcription-PCR, and enzyme-linked immunosorbent assay. Meanwhile, TXL mechanism on AAA was checked by a series of molecular experiments. Also, TXL function on AAA in vivo was further evaluated using hematoxylin-eosin staining, TUNEL assay, Picric acid-Sirius red staining and immunofluorescence assay in C57BL/6 mice. RESULTS: TXL alleviated Ang II-induced VSMC injury mainly by enhancing VSMC proliferation and weakening cell apoptosis, alleviating VSMC inflammation, and reducing extracellular matrix (ECM) degradation of VSMCs. Furthermore, mechanistic studies corroborated that TXL reversed the high levels of Toll-like receptor 4 (TLR4) and p-p65/p65 induced by Ang II. Also, TXL facilitated VSMC proliferation and reduced cell apoptosis, repressed inflammation, and ECM degradation of VSMCs, while these effects were reversed by TLR4 overexpression. In vivo studies further confirmed that TXL owned the function of alleviating AAA, such as alleviating collagen fiber hyperplasia and inflammatory cell infiltration in AAA mice, and repressing inflammation and ECM degradation. CONCLUSION: TXL protected VSMCs against Ang II-induced injury through activating TLR4/noncanonical nuclear factor-kappaB(NF-κB).

Pulmonary artery sarcoma misdiagnosed as a pulmonary embolism: A case report.

Pulmonary artery sarcoma is a rare type of tumor and is easily misdiagnosed. We report a case of pulmonary artery sarcoma in a 26-year-old young man who presented with acute onset of dyspnea. Computed tomographic angiography of the chest had revealed a large filling defect within the main pulmonary artery (PA) that extended into both right and left PAs. Because pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, leading to the resection of the mass. After an uneventful postoperative course, the patient was discharged from the hospital on postoperative day ten. He was subsequently treated with chemotherapy and continued to show no evidence of disease. Multimodal therapy can provide prolonged survival.

Efficacy and safety of low-dose sacubitril/valsartan in heart failure patients: A systematic review and meta-analysis.

BACKGROUND: Controversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF). HYPOTHESIS: Low-dose sacubitril/valsartan might also be effective and safe in HF patients. METHODS: Electronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome. RESULTS: A total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan. CONCLUSIONS: Compared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.

Dynamic Changes in Red Cell Distribution Width Can Predict Major Adverse Cardiovascular Events after PCI in Patients with Unstable Angina Pectoris: A Retrospective Cohort Study.

Background: The increased red cell distribution width (RDW) is related to a higher risk for cardiovascular disease (CVD). However, it is yet unclear whether the dynamic change of RDW is associated with the major adverse cardiovascular events (MACEs) for individual with CVD. Methods and Results: A cohort study was conducted among 228 patients who had unstable angina (UA) and underwent PCI. RDW was measured preceding PCI and re-measured on the 16th week after PCI. The change of RDW values was defined as ΔRDW. The patients were divided into 3 groups in accordance with ΔRDW: improved, stable, and worsened RDW groups. The patients were followed up for 6 years, and MACE episodes were recorded. The survival analysis showed that the incidence of MACEs in stable RDW group was significantly lower than that in improved and worsened RDW groups. By the COX model, the risk of the occurrence of cardiovascular events in improved RDW group was 1.661 times higher than the risk in stable RDW group (HR =1.661, 95% CI: 1.583-2.880, p < 0.05) and the same situation was 3.307 times higher in worsened RDW group (HR =3.307, 95% CI: 1.830-5.041, p < 0.05). Conclusion: The measurement of ΔRDW has potential to predict the MACEs in UA patients underwent PCI. The dynamic changes in RDW are associated with the outcome of CVD.

A Mild Causal Relationship Between Tea Consumption and Obesity in General Population: A Two-Sample Mendelian Randomization Study.

Evidence from observational studies for the effect of tea consumption on obesity is inconclusive. This study aimed to verify the causal association between tea consumption and obesity through a two-sample Mendelian randomization (MR) analysis in general population-based datasets. The genetic instruments, single nucleotide polymorphisms (SNPs) associated with tea consumption habits, were obtained from genome-wide association studies (GWAS): UK Biobank, Nurses' Health Study, Health Professionals Follow-up Study, and Women's Genome Health Study. The effect of the genetic instruments on obesity was analyzed using the UK Biobank dataset (among ∼500,000 participants). The causal relationship between tea consumption and obesity was analyzed by five methods of MR analyses: inverse variance weighted (IVW) method, MR-Egger regression method, weighted median estimator (WME), weighted mode, and simple mode. Ninety-one SNPs were identified as genetic instruments in our study. A mild causation was found by IVW (odds ratio [OR] = 0.998, 95% confidence interval [CI] = 0.996 to 1.000, p = 0.049]), which is commonly used in two-sample MR analysis, indicating that tea consumption has a statistically significant but medically weak effect on obesity control. However, the other four approaches did not show significance. Since there was no heterogeneity and pleiotropy in this study, the IVW approach has the priority of recommendation. Further studies are needed to clarify the effects of tea consumption on obesity-related health problems in detail.

A Rare Case of Primary Malignant Pericardial Mesothelioma Diagnosed with Pericardiotomy.

Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and lethal cardiac tumor. This article presents a 62-year-old man with recurrent pericardial fluid. The patient's clinical symptoms and imaging features were nonspecific. Initial diagnosis was constrictive pericarditis. After admission, the patient's symptoms worsened, and echocardiography indicated increased pericardial effusion. To diagnose and improve the patient's symptoms, pericardiotomy was performed; however, the procedure was unsuccessful because the pericardium was densely adherent to the myocardium. Histopathological examination, including immunohistochemical staining of the pericardial specimen revealed malignant mesothelioma. We recommended adjuvant therapy for the patient with cis-platinum and pemetrexed; however, the patient and his family refused treatment. The patient was discharged 11 days after surgery. The patient survived for more than 15 months with surgical treatment. In this report, the patient's symptoms improved, and the patient survived beyond the median survival after surgical treatment.   Conclusion: The definitive diagnosis of PMPM mostly has been obtained from specimens obtained by surgery. Surgery is an effective treatment method because it prevents cardiac tamponade and can improve symptoms or prognosis, but complete resection is impossible.

ΔRDW: A Novel Indicator with Predictive Value for the Diagnosis and Treatment of Multiple Diseases.

Elevated red blood cell distribution width (RDW) is a powerful predictor of poor prognosis in a variety of diseases, but a single measurement of RDW cannot reflect the dynamic change of diseases. ΔRDW, as a risk stratification tool, can be used to record changes in RDW before and after treatment; also, it allows investigators to name the unit change of RDW in the studied population. So far, there have been few relevant studies on the predictive value of ΔRDW for different diseases; this article aims to review the studies and summaries of the current understandings on the correlation between ΔRDW and disease outcomes.

Sacubitril/valsartan improves cardiac function in Chinese patients with heart failure: a real-world study.

AIMS: Sacubitril/valsartan significantly reduced heart failure (HF) hospitalization and cardiovascular mortality in a randomized controlled trial. However, little is known about real-world efficacy and safety of sacubitril/valsartan in Chinese patients with HF with reduced ejection fraction (HFrEF). We aimed to evaluate whether sacubitril/valsartan could improve cardiac function in Chinese patients with HFrEF in a tertiary hospital in China. METHODS AND RESULTS: Patients with HFrEF receiving sacubitril/valsartan in our hospital between January 2018 and January 2020 were recruited in the present study. We retrospectively collected and analysed all clinical parameters at baseline and during follow-up. A total of 100 consecutive patients (73% male) with HFrEF were recruited in the present study. During a median follow-up period of 365 days [interquartile range (IQR), 346-378], a pronounced improvement of cardiac function was achieved. New York Heart Association classification was significantly improved (P < 0.001), and median N-terminal pro-B-type natriuretic peptides level significantly decreased from 3003 pg/mL (IQR, 1513-5404) to 2039 pg/mL (IQR, 921-3955) (P = 0.010). Mean left ventricular ejection fraction increased from 31 ± 6% to 38 ± 10% (P < 0.001) and median left ventricular end-diastolic diameter reduced from 63 mm (IQR, 59-67) to 60 mm (IQR, 55-68) (P = 0.001). Mean pulmonary arterial systolic pressure decreased significantly from 49 ± 13 mmHg to 44 ± 12 mmHg (P < 0.001) and median right ventricular end-diastolic diameter reduced from 23 mm (IQR, 21-26) to 22 mm (IQR, 20-25) (P = 0.030). After treatment with sacubitril/valsartan, mean estimated glomerular filtration rate significantly decreased (from 88.8 ± 22.4 mL/min to 71.8 ± 27.3 mL/min, P < 0.001). Median serum creatinine and median blood urea nitrogen levels significantly increased [from 0.9 mg/dL (IQR, 0.8-1.0) to 1.1 mg/dL (IQR, 0.9-1.3), P < 0.001, and from 6.8 mmol/L (IQR, 5.5-8.9) to 8.0 mmol/L (IQR, 6.6-10.3), P = 0.002, respectively]. The proportion of patients with chronic kidney disease Stage 3/4 increased significantly from 8% to 39% (P < 0.001). CONCLUSIONS: In Chinese patients with HFrEF, sacubitril/valsartan treatment was associated with a pronounced improvement of cardiac function, but might be prone to a decrease in blood pressure and deterioration in renal function.

S100A1 as a potential biomarker for the diagnosis of patients with acute aortic dissection.

OBJECTIVE: Acute aortic dissection (AAD) is a common life-threatening cardiovascular disease. This retrospective study was conducted to analyze the plasma concentration of S100A1 and its diagnostic value for AAD through receiver operating characteristic (ROC) curve and logistic regression analyses. METHODS: Seventy-eight patients with AAD and 77 healthy controls were included, and the relevant clinical data for each group were collected. According to the Stanford classification, the AAD patients were divided into types A and B. The plasma levels of S100A1, D-dimer, hypersensitive C-reactive protein, and cardiac troponin T were detected by enzyme-linked immunosorbent assays. RESULTS: The S100A1 concentrations in the healthy control, Stanford A, and Stanford B groups were 0.7 ± 0.6, 4.9 ± 2.6, and 3.5 ± 2.2 ng/mL, respectively. The concentration of S100A1 was increased in patients with AAD complicated with aortic regurgitation, pericardial effusion, or in-hospital death. ROC curve analysis showed that the area under the curve was 0.89. Logistic regression analysis revealed that the S100A1 level was an important risk factor for the development of AAD. CONCLUSION: Plasma S100A1 is significantly elevated in patients with AAD, and its concentration has potential clinical value for diagnosing AAD.

Effects of clopidogrel, prasugrel and ticagrelor on prevention of stent thrombosis in patients underwent percutaneous coronary intervention: A network meta-analysis.

BACKGROUND: Clopidogrel, prasugrel and ticagrelor, acting on platelet P2Y12 receptor, are commonly used for prevention of stent thrombosis (ST) among patients who underwent percutaneous coronary intervention (PCI). This study aimed to compare the effects of these drugs by a systematic review and network meta-analysis. HYPOTHESIS: Efficacies of clopidogrel, prasugrel and ticagrelor on preventing ST are not the same. METHODS: PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) that investigated the effect of clopidogrel, prasugrel, or ticagrelor on prevention of ST in patients who underwent PCI. The efficacies between groups were compared by a Bayesian network meta-analysis, by which the pooled odds ratios (ORs) and 95% confidence intervals (CIs) was calculated. RESULTS: Fourteen studies and 46 983 participants were included in this study. The pooled results illustrated that clopidogrel, prasugrel and ticagrelor were effective on prevention of ST. Patients treated with prasugrel (OR = 0.30, 95% CI = 0.052 ~ 0.73, P < 0.05) and ticagrelor (OR = 0.25, 95% CI = 0.035 ~ 0.65, P < 0.05) had lower incidence of ST compared to those treated with clopidogrel. Patients treated with ticagrelor showed similar frequency with those in prasugrel group (OR = 0.86, 95% CI = 0.22 ~ 2.3, P > 0.05). No significant heterogeneity was observed across included studies. CONCLUSIONS: Our findings suggest that prasugrel and ticagrelor are more effective than clopidogrel on prevention of ST among patients underwent PCI. Simultaneously, there is no significant difference in the prevention of ST between prasugrel and ticagrelor.

Salidroside protects against cardiomyocyte apoptosis and ventricular remodeling by AKT/HO-1 signaling pathways in a diabetic cardiomyopathy mouse model.

BACKGROUND: Diabetic cardiomyopathy is characterized by both systolic and diastolic dysfunction due to decreased contractility, as well as reduced compliance of the myocardium. Oxidative stress plays a significant role in diabetes mellitus and its cardiovascular complications. Salidroside, a glucoside of the phenylpropanoid tyrosol, reportedly increases the levels of the antioxidative enzymes, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 (HO-1) to counteract oxidative stress; however, the underlying mechanisms are poorly understood. PURPOSE: Here we investigate the potential cardio-protective effects of salidroside and its mechanism in a diabetic animal model. METHODS: Male db/m, db/db, and age-matched wild-type mice were treated with salidroside at low dose (0.025 mg/kg) or high dose (0.05 mg/kg) by gavage every day for 12 weeks. Cardiac function and structure were assessed by echocardiography and histopathological examination. H9C2 cardiomyocytes were exposed in vitro to advanced glycosylation end products (400 µg/ml) and treated with salidroside (0.1, 1, or 10 µM). The expression of signaling-related genes were explored by western blotting and real-time PCR. RESULTS: Salidroside treatment significantly improved diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis in vivo. Mechanistically, salidroside markedly up-regulates HO-1 expression by activation of the AKT signaling pathway. CONCLUSION: Salidroside protects against cardiomyocyte apoptosis and ventricular remodeling in diabetic mice. This cardio-protective effect of salidroside is dependent on AKT signaling activation.