Publications by authors named "Xiaotong Cui"

26 Publications

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Increased ratio of sST2/LVMI predicted cardiovascular mortality and heart failure rehospitalization in heart failure with reduced ejection fraction patients: a prospective cohort study.

BMC Cardiovasc Disord 2021 08 17;21(1):396. Epub 2021 Aug 17.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction.

Methods: This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model.

Results: Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan-Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm.

Conclusion: In patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.
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http://dx.doi.org/10.1186/s12872-021-02191-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369618PMC
August 2021

Alteration of m6A RNA Methylation in Heart Failure With Preserved Ejection Fraction.

Front Cardiovasc Med 2021 5;8:647806. Epub 2021 Mar 5.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease, in which its pathogenesis is very complex and far from defined. Here, we explored the N-methyladenosine (m6A) RNA methylation alteration in patients with HFpEF and mouse model of HFpEF. In this case-control study, peripheral blood mononuclear cells (PBMCs) were separated from peripheral blood samples obtained from 16 HFpEF patients and 24 healthy controls. The change of m6A regulators was detected by quantitative real-time PCR (RT-PCR). A "two-hit" mouse model of HFpEF was induced by a high-fat diet and drinking water with 0.5 g/L of -nitro-l-arginine methyl ester (L-NAME). MeRIP-seq was used to map transcriptome-wide m6A in control mice and HFpEF mice, and the gene expression was high-throughput detected by RNA-seq. The expression of m6A writers , and ; m6A eraser ; and reader was up-regulated in HFpEF patients, compared with health controls. Furthermore, the expression of was also elevated in HFpEF mice. A total of 661 m6A peaks were significantly changed by MeRIP-seq. Gene Ontology (GO) analysis revealed that protein folding, ubiquitin-dependent ERAD pathway, and positive regulation of RNA polymerase II were the three most significantly altered biological processes in HFpEF. The pathways including proteasome, protein processing in the endoplasmic reticulum, and PI3K-Akt signaling pathway were significantly changed in HFpEF by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression pattern of m6A regulators and m6A landscape is changed in HFpEF. This uncovers a new transcription-independent mechanism of translation regulation. Therefore, our data suggest that the modulation of epitranscriptomic processes, such as m6A methylation, might be an interesting target for therapeutic interventions.
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http://dx.doi.org/10.3389/fcvm.2021.647806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973040PMC
March 2021

Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes.

J Am Heart Assoc 2021 04 17;10(7):e015292. Epub 2021 Mar 17.

Department of Cardiology Shanghai Institute of Cardiovascular DiseasesZhongshan HospitalFudan University Shanghai China.

Background Small intestinal bacterial overgrowth (SIBO) is a common pathological condition of intestinal microbiota. The prevalence of SIBO and its prognostic value in patients with heart failure (HF) are unknown. Methods and Results A total of 287 patients tested for SIBO using lactulose hydrogen-methane breath test were evaluated. At least 1 of the following criteria fulfilled was SIBO positive: patients with fasting hydrogen level ≥20 parts per million (ppm) or a ≥20 ppm rise in hydrogen by 90 minutes were diagnosed with SIBO (H) positive; and patients with methane levels ≥10 ppm at any test point were diagnosed with SIBO (CH) positive. The association between SIBO and the composite of cardiovascular death and HF rehospitalization was investigated. In 287 consecutive patients with HF, 128 (45%) were positive for SIBO. Our result showed SIBO increased the risk of HF rehospitalization in patients with HF with reduced ejection fraction (<0.001), and the risk of cardiovascular death in patients with HF with preserved EF (=0.011). SIBO was an independent risk factor of primary end point in patients with HF (hazard ratio [HR], 2.13; 95% CI; 1.26-3.58; =0.005). In addition, SIBO (CH) showed a prognostic value on adverse outcomes (HR, 2.35; 95% CI, 1.38-4.02; <0.001), whereas the association between SIBO (H) and outcomes was not statistically significant. Conclusions There was high prevalence of SIBO in patients with HF, and SIBO was independently associated with poor outcomes. Proactive treatment for SIBO may provide extra benefit for patients with HF.
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http://dx.doi.org/10.1161/JAHA.119.015292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174348PMC
April 2021

Hospital readmissions of patients with heart failure from real world: timing and associated risk factors.

ESC Heart Fail 2021 04 17;8(2):1388-1397. Epub 2021 Feb 17.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Aims: This study aims to investigate hospital readmissions and timing, as well as risk factors in a real world heart failure (HF) population.

Methods And Results: All patients discharged alive in 2016 from Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, with a primary diagnosis of HF were consecutively included. Patient characteristics, type of HF, treatment, and follow-up were registered. Time to first all-cause or HF readmission, as well as number of 1 year readmissions from discharge were recorded. In total, 448 patients were included: 273 patients (mean age 78 ± 11.8 years) were readmitted for any cause within 1 year (readmission rate of 60.9%), and 175 patients (mean age 76.6 ± 13.7) were never readmitted. Among readmissions, 60.1% occurred during the first quarter after index hospitalization, giving a 3 month all-cause readmission rate of 36.6%. HF-related 1 year readmission rate was 38.4%. Patients who were readmitted had significantly more renal dysfunction (52.4% vs. 36.6%, P = 0.001), pulmonary disease (25.6% vs. 15.4%, P = 0.010), and psychiatric illness (24.9% vs. 12.0%, P = 0.001). Number of co-morbidities and readmissions were significantly associated (P < 0.001 for all cause readmission rate and P = 0.012 for 1 year HF readmission rate). Worsening HF constituted 63% of all-cause readmissions. Psychiatric disease was an independent risk factor for 1 month and 1 year all-cause readmissions. Poor compliance to medication was an independent risk factor for 1 month and 1 year HF readmission.

Conclusions: In our real world cohort of HF patients, frequent hospital readmissions occurred in the early post-discharge period and were mainly driven by worsening HF. Co-morbidity was one of the most important factors for readmission.
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http://dx.doi.org/10.1002/ehf2.13221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006673PMC
April 2021

Guideline-directed medical therapy in real-world heart failure patients with low blood pressure and renal dysfunction.

Clin Res Cardiol 2021 Jul 4;110(7):1051-1062. Epub 2021 Jan 4.

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Background: Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), β-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction.

Methods: This study initially included 51, 060 HF patients from the Swedish Heart Failure Registry, and finally 1464 HFrEF patients with low BP (systolic BP ≦ 100 mmHg) and renal dysfunction (estimated glomerular filtration rate (eGFR) ≦ 60 ml/min/1.73m) were ultimately enrolled. Patients were receiving oral medication for HF at study enrollment, and divided into four groups (group 1-4: ACEI/ARB + BB + MRA, ACEI/ARB + BB, ACEI/ARB + MRA or ACEI/ARB only, and other). The outcome is time to all-cause mortality.

Results: Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1-4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89-1.21) (p = 0.62), group 3 1.40 (1.09-1.79) (p = 0.009), and group 4 1.71 (1.39-2.09) (p < 0.001).

Conclusions: In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.
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http://dx.doi.org/10.1007/s00392-020-01790-yDOI Listing
July 2021

Prescription Promotes Angiogenesis of Hypoxic Primary Rat Cardiac Microvascular Endothelial Cells via Regulating miR-21 Signaling.

Curr Pharm Des 2021 ;27(26):2966-2974

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 200032, Shanghai, China.

Background And Objective: Angiogenesis is the most important repair process of tissues subjected to ischemic injury. The present study aims to investigate whether the pro-angiogenic effect of Qiliqiangxin prescription (QL) is mediated through miR-21 signaling.

Methods: Cardiac microvascular endothelial cells (CMECs) were isolated and cultured from 2-3 weeks old SD rats by the method of planting myocardium tissues. The purity was identified by CD31 immunofluorescence staining. CMECs were then cultured under 1% O2 hypoxia or normoxia condition for 24h in the presence or absence of QL pretreatment (QL, 0.5mg/ml, 24h). The mimics and inhibitors of miR-21 were transfected into CMECs. miR-21, HIF-1α, and VEGF expressions of CMECs were then detected by qRT-PCR and/or Western blot. The proliferation, migration, and tube formation functions of CMECs were assessed using the BrdU assay, wound healing test, and tube formation assay, respectively.

Results: The results showed that compared with the control group, hypoxia significantly upregulated the expression of miR-21 and impaired CMECs proliferation, migration, and tube formation functions. Compared with the hypoxia group, QL further upregulated miR-21, HIF-1α, and VEGF expressions, and improved cell proliferation, migration, and tube formation of hypoxic CMECs. These effects of QL were abolished by a knockdown of miR-21. Conversely, treatment with miR-21 mimics further enhanced QL induced changes in hypoxic CMECs.

Conclusion: Results indicate that the pro-angiogenesis effects of QL on hypoxic CMECs are mediated by activating miR-21 and its downstream HIF-1α/VEGF pathway possibly.
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http://dx.doi.org/10.2174/1381612826666201005152709DOI Listing
January 2021

Trends in cause-specific readmissions in heart failure with preserved vs. reduced and mid-range ejection fraction.

ESC Heart Fail 2020 10 30;7(5):2894-2903. Epub 2020 Jul 30.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Aims: The aim of this study was to investigate whether the readmission of heart failure (HF) patients has decreased over time and how it differs among HF with preserved ejection fraction (EF) (HFpEF) vs. reduced EF (HFrEF) and mid-range EF (HFmrEF).

Methods And Results: We evaluated HF patients index hospitalized from January 2004 to December 2011 in the Swedish Heart Failure Registry with 1 year follow-up. Outcome measures were the first occurring all-cause, cardiovascular (CV), and HF readmissions. A total of 20 877 HF patients (11 064 HFrEF, 4215 HFmrEF, and 5562 HFpEF) were included in the study. All-cause readmission was the highest in patients with HFpEF, whereas CV and HF readmissions were the highest in HFrEF. From 2004 to 2011, HF readmission rates within 6 months (from 22.3% to 17.3%, P = 0.003) and 1 year (from 27.7% to 23.4%, P = 0.019) in HFpEF declined, and the risk for 1 year HF readmission in HFpEF was reduced by 7% after adjusting for age and sex (P = 0.022). Likewise, risk factors for HF readmission in HFpEF changed. However, no significant changes were observed in all-cause or CV readmission rates in HFpEF, and no significant changes in cause-specific readmissions were observed in HFrEF. Time to the first readmission did not change significantly from 2004 to 2011, regardless of EF subgroup (all P-values > 0.05).

Conclusions: Declining temporal trend in HF readmission rates was found in HFpEF, but all-cause readmission still remained the highest in HFpEF vs. HFrEF and HFmrEF. More efforts are needed to reduce the non-HF-related readmission in patients with HFpEF.
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http://dx.doi.org/10.1002/ehf2.12899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524131PMC
October 2020

The impact of time-updated resting heart rate on cause-specific mortality in a random middle-aged male population: a lifetime follow-up.

Clin Res Cardiol 2021 Jun 21;110(6):822-830. Epub 2020 Jul 21.

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.

Background: A high resting heart rate (RHR) is associated with an increase in adverse events. However, the long-term prognostic value in a general population is unclear. We aimed to investigate the impact of RHR, based on both baseline and time-updated values, on mortality in a middle-aged male cohort.

Methods: A random population sample of 852 men, all born in 1913, was followed from age 50 until age 98, with repeated examinations including RHR over a period of 48 years. The impact of baseline and time-updated RHR on cause-specific mortality was assessed using Cox proportional hazard models and cubic spline models.

Results: A baseline RHR of ≥ 90 beats per minute (bpm) was associated with higher all-cause mortality, as compared with an RHR of 60-70 bpm (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.17-2.19, P = 0.003), but not with cardiovascular (CV) mortality. A time-updated RHR of < 60 bpm (HR 1.41, 95% CI 1.07-1.85, P = 0.014) and a time-updated RHR of 70-80 bpm (HR 1.34, 95% CI 1.02-1.75, P = 0.036) were both associated with higher CV mortality as compared with an RHR of 60-70 bpm after multivariable adjustment. Analyses using cubic spline models confirmed that the association of time-updated RHR with all-cause and CV mortality complied with a U-shaped curve with 60 bpm as a reference.

Conclusion: In this middle-aged male cohort, a time-updated RHR of 60-70 bpm was associated with the lowest CV mortality, suggesting that a time-updated RHR could be a useful long-term prognostic index in the general population.
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http://dx.doi.org/10.1007/s00392-020-01714-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166682PMC
June 2021

An Effective Simulation Analysis of Transient Electromagnetic Multiple Faults.

Sensors (Basel) 2020 Apr 1;20(7). Epub 2020 Apr 1.

Faculty of Engineering, University Malaysia Sabah, Kota Kinabalu 88400, Malaysia.

Embedded encryption devices and smart sensors are vulnerable to physical attacks. Due to the continuous shrinking of chip size, laser injection, particle radiation and electromagnetic transient injection are possible methods that introduce transient multiple faults. In the fault analysis stage, the adversary is unclear about the actual number of faults injected. Typically, the single-nibble fault analysis encounters difficulties. Therefore, in this paper, we propose novel ciphertext-only impossible differentials that can analyze the number of random faults to six nibbles. We use the impossible differentials to exclude the secret key that definitely does not exist, and then gradually obtain the unique secret key through inverse difference equations. Using software simulation, we conducted 32,000 random multiple fault attacks on Midori. The experiments were carried out to verify the theoretical model of multiple fault attacks. We obtain the relationship between fault injection and information content. To reduce the number of fault attacks, we further optimized the fault attack method. The secret key can be obtained at least 11 times. The proposed ciphertext-only impossible differential analysis provides an effective method for random multiple faults analysis, which would be helpful for improving the security of block ciphers.
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http://dx.doi.org/10.3390/s20071976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181125PMC
April 2020

Exercise improves cardiac function and glucose metabolism in mice with experimental myocardial infarction through inhibiting HDAC4 and upregulating GLUT1 expression.

Basic Res Cardiol 2020 03 31;115(3):28. Epub 2020 Mar 31.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

This study aims to determine the effect of exercise on the cardiac function, metabolic profiles and related molecular mechanisms in mice with ischemic-induced heart failure (HF). HF was induced by myocardial infarction (MI) in C57BL6/N mice. Cardiac function and physical endurance were improved in HF mice after exercise. Micro-PET/CT scanning revealed enhanced myocardial glucose uptake in vivo in HF mice after exercise. Exercise reduced mitochondrial structural damage in HF mice. Cardiomyocytes isolated from HF + exercise mice showed increased glycolysis capacity, respiratory function and ATP production. Both mRNA and protein expression of glucose transporter 1 (GLUT1) were upregulated after exercise. Results of ChIP-PCR revealed a novel interaction between transcription factor myocyte enhancer factor 2a (MEF2a) and GLUT1 in hearts of HF + exercise mice. Exercise also activated myocardial AMP-activated protein kinase (AMPK), which in turn phosphorylated histone deacetylase 4 (HDAC4), and thereby modulated the GLUT1 expression through reducing its inhibition on MEF2a in HF mice. Inhibition of HDAC4 also improved cardiac function in HF mice. Moreover, knockdown of GLUT1 impaired the systolic and diastolic function of isolated cardiomyocytes. In conclusion, exercise improves cardiac function and glucose metabolism in HF mice through inhibiting HDAC4 and upregulating GLUT1 expression.
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http://dx.doi.org/10.1007/s00395-020-0787-1DOI Listing
March 2020

Temporal trends in cause-specific readmissions and their risk factors in heart failure patients in Sweden.

Int J Cardiol 2020 05 22;306:116-122. Epub 2020 Feb 22.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: It remains unclear whether readmissions of patients with heart failure (HF) have decreased over time in an era of improved therapy and management of HF. This study aimed to determine the temporal short- and long-term trends of cause-specific rehospitalization and their risk factors in a Swedish context.

Methods: HF patients in the Swedish Heart Failure Registry (SwedeHF) were investigated. Maximum follow-up time was 1 year. Outcomes included the first occurrence of all-cause, cardiovascular (CV) and HF rehospitalizations. Cox proportional hazards models were performed to determine the impact of increasing years on risk for rehospitalization and its known risk factors.

Results: Totally, 25,644 index-hospitalized HF patients in SwedeHF from 2004 to 2011 were enrolled in the study. For 8 years, the incidence risk of 1-year all-cause rehospitalization remained unchanged, whereas the incidence risk of CV (P = 0.038) or HF (P = 0.0038) rehospitalization decreased. After adjustment for age and sex, a 3% decrease per every second year was observed for 1-year CV and HF rehospitalizations (P < 0.05). However, time to the first occurring all-cause, CV and HF rehospitalization did not change significantly from 2004 to 2011 (P-values 0.13-0.87). When two study periods (2004-2005 vs. 2010-2011) were compared, the risk factor profile for rehospitalization was found to change.

Conclusions: Throughout the 8-year study period, CV- and HF-related rehospitalizations decreased, whereas all-cause rehospitalization remained unchanged, indicating a parallel increase in non-CV rehospitalization in the HF patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.02.048DOI Listing
May 2020

Diffuse myocardial fibrosis and the prognosis of heart failure with reduced ejection fraction in Chinese patients: a cohort study.

Int J Cardiovasc Imaging 2020 Apr 1;36(4):671-689. Epub 2020 Jan 1.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Evidence regarding the relationship between diffuse myocardial fibrosis and the prognosis of heart failure with reduced ejection fraction (HFrEF) was limited. Therefore, this study set out to investigate whether diffuse myocardial fibrosis was independently related to the prognosis of failure with reduced ejection fraction in Chinese patients after adjusting for other covariates. The present study was a cohort study. A total of 45 consecutive HFrEF patients were involved in Zhongshan Hospital of Fudan University in China from 1/9/2015 to 31/12/2016. The target-independent variable was extracellular volume (ECV) quantified by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence at baseline. To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Covariates involved in this study included age, gender, body mass index, heart rate, systolic blood pressure diastolic blood pressure, smoking, hypertension, diabetes mellitus, etiology, NYHA functional class, blood urea nitrogen, creatinine, serum uric acid, total bilirubin, and growth stimulation-expressed gene 2. Ten age- and sex-matched healthy participants with no history of cardiovascular disease served as a control group. Mean MOLLI-ECV was significantly higher in HFrEF patients versus healthy controls (29.55 ± 1.46% vs. 23.17 ± 1.93%, P < 0.001). Patients were followed for 9 months, during which the primary outcome (cardiac death or first heart failure hospitalization) occurred in 15 patients. By Kaplan-Meier analysis, patients with high MOLLI-ECV ≥ 30.10% had shorter event-free survival than the middle (MOLLI-ECV between 30.10 and 28.60) and low (MOLLI-ECV < 28.60) MOLLI-ECV patients (log-rank, P = 0.0035). Result of fully-adjusted multivariable Cox regression analysis showed MOLLI-ECV was positively associated with the composite outcome of HFrEF patients after adjusting confounders hazard ratio (HR) 2.57, 95% CI (1.09, 6.04). By subgroup analysis, a stronger association was seen in patients who with NYHA functional class III-IV, hematocrit < 39.8%, left atrial diameter ≥ 53.5 mm, or without the medical history of MRA or diuretics other than MRA. The P for interaction was < 0.05. In HFrEF patients, the relationship between MOLLI-ECV determined by CMR and the composite outcome is linear. High MOLLI-ECV was associated with a higher rate of cardiac mortality and first HF hospitalization in the short term follow up.
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http://dx.doi.org/10.1007/s10554-019-01752-0DOI Listing
April 2020

A Novel Multi-Objective Electromagnetic Analysis Based on Genetic Algorithm.

Sensors (Basel) 2019 Dec 15;19(24). Epub 2019 Dec 15.

Electrical Engineering Department, Bahauddin Zakariya University, Multan 60000, Pakistan.

Correlation electromagnetic analysis (CEMA) is a method prevalent in side-channel analysis of cryptographic devices. Its success mostly depends on the quality of electromagnetic signals acquired from the devices. In the past, only one byte of the key was analyzed and other bytes were regarded as noise. Apparently, other bytes' useful information was wasted, which may increase the difficulty of recovering the key. Multi-objective optimization is a good way to solve the problem of a single byte of the key. In this work, we applied multi-objective optimization to correlation electromagnetic analysis taking all bytes of the key into consideration. Combining the advantages of multi-objective optimization and genetic algorithm, we put forward a novel multi-objective electromagnetic analysis based on a genetic algorithm to take full advantage of information when recovering the key. Experiments with an Advanced Encryption Standard (AES) cryptographic algorithm on a Sakura-G board demonstrate the efficiency of our method in practice. The experimental results show that our method reduces the number of traces required in correlation electromagnetic analysis. It achieved approximately 42.72% improvement for the corresponding case compared with CEMA.
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http://dx.doi.org/10.3390/s19245542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960805PMC
December 2019

Impact of immobilization technology in industrial and pharmaceutical applications.

3 Biotech 2019 Dec 8;9(12):440. Epub 2019 Nov 8.

1College of Grain Science and Technology, Shenyang Normal University, Number 253 North Yellow River Road, Shenyang, 110034 China.

The current demands of the world's biotechnological industries are enhancement in enzyme productivity and development of novel techniques for increasing their shelf life. Compared to free enzymes in solution, immobilized enzymes are more robust and more resistant to environmental changes. More importantly, the heterogeneity of the immobilized enzyme systems allows an easy recovery of both enzymes and products, multiple reuse of enzymes, continuous operation of enzymatic processes, rapid termination of reactions, and greater variety of bioreactor designs. This review summarizes immobilization definition, different immobilization methods, advantages and disadvantages of each method. In addition, it covers some food industries, protein purification, human nutrition, biodiesel production, and textile industry. In these industries, the use of enzymes has become an inevitable processing strategy when a perfect end product is desired. It also can be used in many other important industries including health care and pharmaceuticals applications. One of the best uses of enzymes in the modern life is their application in diagnose and treatment of many disease especially when used in drug delivery system or when used in nanoform.
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http://dx.doi.org/10.1007/s13205-019-1969-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841786PMC
December 2019

Effects of Adiponectin on Diastolic Function in Mice Underwent Transverse Aorta Constriction.

J Cardiovasc Transl Res 2020 04 16;13(2):225-237. Epub 2019 Oct 16.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). Nevertheless, the effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. Here, we demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. Notably, APN also improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Moreover, APN supplementation suppressed TAC-induced oxidative stress. In vitro, inhibition of AMPK by compound C (Cpc) abrogated the effect of APN on modulation of titin isoform shift and the anti-hypertrophic effect of APN on cardiomyocytes induced by AngII. In summary, our findings indicate that APN could attenuate diastolic dysfunction in TAC mice, which are at least partially mediated by AMPK pathway.
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http://dx.doi.org/10.1007/s12265-019-09913-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166206PMC
April 2020

Angiotensin II induces apoptosis of cardiac microvascular endothelial cells via regulating PTP1B/PI3K/Akt pathway.

In Vitro Cell Dev Biol Anim 2019 Dec 9;55(10):801-811. Epub 2019 Sep 9.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Endothelial cell apoptosis and renin-angiotensin-aldosterone system (RAAS) activation are the major pathological mechanisms for cardiovascular disease and heart failure; however, the interaction and mechanism between them remain unclear. Investigating the role of PTP1B in angiotensin II (Ang II)-induced apoptosis of primary cardiac microvascular endothelial cells (CMECs) may provide direct evidence of the link between endothelial cell apoptosis and RAAS. Isolated rat CMECs were treated with different concentrations of Ang II to induce apoptosis, and an Ang II concentration of 4 nM was selected as the effective dose for the subsequent studies. The CMECs were cultured for 48 h with or without Ang II (4 nM) in the absence or presence of the PTP1B inhibitor TCS 401 (8 μM) and the PI3K inhibitor LY294002 (10 μM). The level of CMEC apoptosis was assessed by TUNEL staining and caspase-3 activity. The protein expressions of PTP1B, PI3K, Akt, p-Akt, Bcl-2, Bax, caspase-3, and cleaved caspase-3 were determined by Western blot (WB). The results showed that Ang II increased apoptosis of CMECs, upregulated PTP1B expression, and inhibited the PI3K/Akt pathway. Furthermore, cotreatment with PTP1B inhibitor significantly decreased the number of apoptotic CMECs induced by Ang II, along with increased PI3K expression, phosphorylation of Akt and the ratio of Bcl-2/Bax, decreased caspase-3 activity, and a cleaved caspase-3/caspase-3 ratio, while treatment with LY294002 partly inhibited the anti-apoptotic effect of the PTP1B inhibitor. Ang II induces apoptosis of primary rat CMECs via regulating the PTP1B/PI3K/Akt pathway.
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http://dx.doi.org/10.1007/s11626-019-00395-8DOI Listing
December 2019

Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia.

Mucosal Immunol 2018 07 25;11(4):1203-1218. Epub 2018 Apr 25.

Laboratory of Infection and Prevention, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, 253 Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary immune responses mediated by a variety of immune cells are coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and immune cells, plays an essential role in coordinating innate responses and adaptive immunity against P. aeruginosa infection. Intratracheal treatment of mice with heat-killed P. aeruginosa resulted in prolonged disappearance of Regnase-1 consistent with sustained expression of Regnase-1 target inflammatory genes, whereas the transcription factor NF-κB was only transiently activated. AEC-specific deletion of Regnase-1 not only augmented innate defenses against P. aeruginosa but also enhanced secretion of Pseudomonas-specific IgA and Th17 accumulation in the lung, culminating in conferring significant resistance against P. aeruginosa re-infection in vivo. Although Regnase-1 directly controls distinct sets of genes in each of AECs and T cells, degradation of Regnase-1 in both cell types is beneficial for maximizing acquired immune responses. Collectively, these results demonstrate that Regnase-1 orchestrates AEC-mediated and immune cell-mediated host defense against pulmonary bacterial infection.
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http://dx.doi.org/10.1038/s41385-018-0024-5DOI Listing
July 2018

Regnase-1 and Roquin Nonredundantly Regulate Th1 Differentiation Causing Cardiac Inflammation and Fibrosis.

J Immunol 2017 12 10;199(12):4066-4077. Epub 2017 Nov 10.

Laboratory of Infection and Prevention, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

Regnase-1 and Roquin are RNA binding proteins that are essential for degradation of inflammatory mRNAs and maintenance of immune homeostasis. Although deficiency of either of the proteins leads to enhanced T cell activation, their functional relationship in T cells has yet to be clarified because of lethality upon mutation of both Regnase-1 and Roquin. By using a Regnase-1 conditional allele, we show that mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells. Interestingly, Regnase-1 and Roquin double-mutant mice suffered from severe inflammation and early formation of fibrosis, especially in the heart, along with the increased expression of , but not or Consistently, mutation of both Regnase-1 and Roquin leads to a huge increase in the Th1, but not the Th2 or Th17, population in spleens compared with T cells with a single Regnase-1 or Roquin deficiency. Regnase-1 and Roquin are capable of repressing the expression of a group of mRNAs encoding factors involved in Th1 differentiation, such as and , via their 3' untranslated regions. Moreover, Regnase-1 is capable of repressing Roquin mRNA. This cross-regulation may contribute to the synergistic control of T cell activation/polarization. Collectively, our results demonstrate that Regnase-1 and Roquin maintain T cell immune homeostasis and regulate Th1 polarization synergistically.
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http://dx.doi.org/10.4049/jimmunol.1701211DOI Listing
December 2017

Prevalence and correlates of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in elderly community residents.

Int J Cardiol 2017 Jan 17;227:820-825. Epub 2016 Oct 17.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address:

Background: Left ventricular diastolic dysfunction (LVDD) is closely related to heart failure with preserved ejection fraction (HFpEF), while the prevalence and correlates of either LVDD or HFpEF in elderly population remain largely unknown.

Methods: The study was performed in 1274 community residents (769 women, aged ≥65years) who participated in the Shanghai Heart Health Study. Demographic, laboratory and echocardiographic data were obtained to analyze correlates of LVDD and HFpEF using univariate and multivariate Logistic analysis.

Results: LVDD was detected in 31.9% (406/1274) residents and it was significantly higher in women than in men (34.2% vs. 28.3%, P=0.027). HFpEF prevalence was 2.8% (35/1274), and increased with aging in the whole cohort. For residents with left ventricular ejection fraction ≥50% and normal-sized ventricular cavity, female sex (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.24-2.29), heart rate (OR 0.76, 95% CI 0.68-0.86), atrial fibrillation (OR 7.37, 95% CI 3.13-17.36), hypertension (OR 1.32, 95% CI 1.00-1.75), N-terminal pro-B type natriuretic peptide (OR 2.33, 95% CI 1.50-3.61) and high-sensitivity troponin T (hs-TnT) (OR 1.90, 95% CI 1.12-3.23) were independent correlates of asymptomatic LVDD. While age (OR 1.44, 95% CI 1.01-2.06), heart rate (OR 0.66, 95% CI 0.47-0.93) and hs-TnT (OR 4.37, 95% CI 1.46-13.12) were independently related to HFpEF.

Conclusions: LVDD is common in this community elderly population, and HFpEF is also not rare. Different factors played roles in different stages of HFpEF. Future studies are warranted to explore the predictors of LVDD and HFpEF in the community elderly.
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http://dx.doi.org/10.1016/j.ijcard.2016.10.041DOI Listing
January 2017

Research on torsional friction behavior and fluid load support of PVA/HA composite hydrogel.

J Mech Behav Biomed Mater 2016 09 13;62:182-194. Epub 2016 May 13.

School of Materials Science and Engineering, China University of Mining and Technology, Xuzhou 221116, China.

Hydrogels have been extensively studied for use as synthetic articular cartilage. This study aimed to investigate (1) the torsional friction contact state and the transformation mechanism of PVA/HA composite hydrogel against CoCrMo femoral head and (2) effects of load and torsional angle on torsional friction behavior. The finite element method was used to study fluid load support of PVA/HA composite hydrogel. Results show fluid loss increases gradually of PVA/HA composite hydrogel with torsional friction time, leading to fluid load support decreases. The contact state changes from full slip state to stick-slip mixed state. As the load increases, friction coefficient and adhesion zone increase gradually. As the torsional angle increases, friction coefficient and slip trend of the contact interface increase, resulting in the increase of the slip zone and the reduction of the adhesion zone. Fluid loss increases of PVA/HA composite hydrogel as the load and the torsional angle increase, which causes the decrease of fluid load support and the increase of friction coefficient.
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http://dx.doi.org/10.1016/j.jmbbm.2016.04.034DOI Listing
September 2016

[The epidemiological profile of heart failure patients in China].

Zhonghua Xin Xue Guan Bing Za Zhi 2015 Dec;43(12):1018-21

Email:

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December 2015

Clinical characteristics, treatment and survival in patients with systolic heart failure--comparative assessment of a Chinese and a German cohort.

Int J Cardiol 2014 Oct 10;176(3):1388-90. Epub 2014 Aug 10.

Department of Medicine I, University Hospital Würzburg and Comprehensive Heart Failure Center, University of Würzburg, 97078 Würzburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.08.026DOI Listing
October 2014

Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

J Cardiovasc Pharmacol 2014 Mar;63(3):218-26

*Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; †Department of Medicine, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden; and ‡Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Objective: To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway.

Methods: Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected.

Results: Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E', decreased E/A and E'/A', while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P < 0.05). Meanwhile, both calcineurin and NFAT3 expressions were downregulated in olmesartan group compared with the other 2 groups (both P < 0.05).

Conclusions: These data suggest the beneficial effect of olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.
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http://dx.doi.org/10.1097/FJC.0000000000000038DOI Listing
March 2014

Association of renal biochemical parameters with left ventricular diastolic dysfunction in a community-based elderly population in China: a cross-sectional study.

PLoS One 2014 12;9(2):e88638. Epub 2014 Feb 12.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Relationship of left ventricular diastolic dysfunction (LVDD) with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population.

Methods: 1,166 community residents (aged ≥ 65 years, 694 females) participating in the Shanghai Heart Health Study with complete data of renal parameters were investigated. Echocardiography was used to evaluate diastolic function with conventional and tissue Doppler imaging techniques. Serum urea, creatinine, urea-to-creatinine ratio, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were analyzed on their associations with LVDD.

Results: The prevalence of LVDD increased in proportion to increasing serum urea, urea-to-creatinine ratio and UACR. These three renal parameters were found negatively correlated to peak early (E) to late (A) diastolic velocities ratio (E/A), and positively to left atrial volume index; UACR also positively correlated with E to peak early (E') diastolic mitral annular velocity ratio (E/E'). Serum urea, urea-to-creatinine ratio and UACR correlated with LVDD in logistic univariate regression analysis, and urea-to-creatinine ratio remained independently correlated to LVDD [Odds ratio (OR) 2.82, 95% confidence interval (CI) 1.34-5.95] after adjustment. Serum urea (OR 1.18, 95%CI 1.03-1.34), creatinine (OR 6.53, 95%CI 1.70- -25.02), eGFR (OR 0.22, 95%CI 0.07-0.65) and UACR (OR 2.15, 95%CI 1.42-3.24) were revealed independent correlates of advanced (moderate and severe) LVDD.

Conclusions: Biochemical parameters of renal function were closely linked with LVDD. This finding described new cardio-renal relationship in the elderly population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088638PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922995PMC
January 2015

Plasma N-terminal pro-brain natriuretic peptide levels predict new-onset atrial fibrillation in patients with acute myocardial infarction.

Int J Cardiol 2013 Oct 4;168(3):3135-7. Epub 2013 May 4.

Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

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http://dx.doi.org/10.1016/j.ijcard.2013.04.032DOI Listing
October 2013
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