Publications by authors named "Qinghua Han"

33 Publications

Survey on sodium and potassium intake in patients with hypertension in China.

J Clin Hypertens (Greenwich) 2021 Sep 25. Epub 2021 Sep 25.

Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Sodium and potassium intake in hypertensive patients in China is not clear. The authors aimed to investigate the distribution of sodium and potassium intake in hypertensive patients in China, and to analyze the relationship between sodium and potassium intake and blood pressure. The study was performed in 130 hospitals from 23 provinces across China from 2016 to 2019. Finally, 9501 hypertensive patients average aged 54 years were included. 24 h urinary sodium and potassium excretion were measured. Distribution of urinary electrolytes were described according to age, gender and region. The association between urinary electrolytes and blood pressure was analyzed by multivariate linear regression. Hypertensive patients exhibited an average 24 h urinary sodium and potassium excretion of 156.7 ± 81.5 mmol/d and 39.2 ± 20.2 mmol/d (equivalent to sodium chloride of 9.2 g/d, potassium chloride of 2.9 g/d), sodium/potassium ratio (median) of 4.14 (2.92,5.73). Urinary electrolytes were lower in women than men (sodium: 171.1 vs 138.7, p < .05; potassium: 40.3 vs 37.7, p < .05), in the elderly than in the younger (sodium: 168.7 vs 139.9, p < .05; potassium: 39.5 vs. 37.5, p < .05). For every 1 unit of Na/K ratio increase, blood pressure increased by 0.46/0.24 mmHg. Blood pressure was 2.75/1.27 mmHg higher in quartile 4 than quartile 1 of Na/K. It remains high sodium and low potassium for hypertensive patients in China. Decreased sodium, Na/K ratio and increased potassium may help for blood pressure management.
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http://dx.doi.org/10.1111/jch.14355DOI Listing
September 2021

Bicaudal-C protein, a potential antidepressant target.

Neuroreport 2021 11;32(16):1293-1298

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.

Bicaudal-C protein is a highly conserved RNA binding protein, which contains K homology domains and sterile alpha motif domain. Genome-wide association study identified that Bicaudal-C protein was associated with depression. The expression of Bicaudal-C increased in depression patients, also increased expression of Bicaudal-C induces the behavior of depression. The decrease of synaptic plasticity plays a part in depression. Bicaudal-C protein reduces the synaptic plasticity of neurons via TrkB/mTOR/AMPA/pGluA1 pathways, Wnt pathway, or influencing some proteins related to synaptic plasticity. The decreased expression of Bicaudal-C plays an important role in the action of several antidepressants, such as ketamine, biperiden, and scopolamine. Therefore, Bicaudal-C protein may be a potential antidepressant target. Clarifying the relationship between Bicaudal-C protein and depression may help us to find new antidepressants. This review focuses on the research advances of the relationship between Bicaudal-C protein and depression.
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http://dx.doi.org/10.1097/WNR.0000000000001729DOI Listing
November 2021

Interpretable prediction of 3-year all-cause mortality in patients with heart failure caused by coronary heart disease based on machine learning and SHAP.

Comput Biol Med 2021 10 28;137:104813. Epub 2021 Aug 28.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Shanxi Medical University, Taiyuan, People's Republic of China. Electronic address:

Background: This study sought to evaluate the performance of machine learning (ML) models and establish an explainable ML model with good prediction of 3-year all-cause mortality in patients with heart failure (HF) caused by coronary heart disease (CHD).

Methods: We established six ML models using follow-up data to predict 3-year all-cause mortality. Through comprehensive evaluation, the best performing model was used to predict and stratify patients. The log-rank test was used to assess the difference between Kaplan-Meier curves. The association between ML risk and 3-year all-cause mortality was also assessed using multivariable Cox regression. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) method was deployed to calculate 3-year all-cause mortality risk and to generate individual explanations of the model's decisions.

Results: The best performing extreme gradient boosting (XGBoost) model was selected to predict and stratify patients. Subjects with a higher ML score had a high hazard of suffering events (hazard ratio [HR]: 10.351; P < 0.001), and this relationship persisted with a multivariable analysis (adjusted HR: 5.343; P < 0.001). Age, N-terminal pro-B-type natriuretic peptide, occupation, New York Heart Association classification, and nitrate drug use were important factors for both genders.

Conclusions: The ML-based risk stratification tool was able to accurately assess and stratify the risk of 3-year all-cause mortality in patients with HF caused by CHD. ML combined with SHAP could provide an explicit explanation of individualized risk prediction and give physicians an intuitive understanding of the influence of key features in the model.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104813DOI Listing
October 2021

Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer.

Acta Pharm Sin B 2021 Jul 21;11(7):1853-1866. Epub 2021 Jan 21.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics pharmacologically targeting molecular motor. Here, we found J13 could directly target myosin-9 (MYH9)-actin molecular motor to promote mitochondrial fission progression, and markedly inhibited cancer cells survival, proliferation and migration. Mechanism study revealed that J13 impaired MYH9-actin interaction to inactivate molecular motor, and caused a cytoskeleton-dependent mitochondrial dynamics imbalance. Moreover, stable isotope labeling with amino acids in cell culture (SILAC) technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9-actin molecular motor to mitochondrial fission. Taken together, we reported the first natural small-molecule directly targeting MYH9-actin molecular motor for anti-cancer translational research. Besides, our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.
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http://dx.doi.org/10.1016/j.apsb.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343112PMC
July 2021

Distal Transradial Access in Anatomical Snuffbox for Coronary Angiography and Intervention: An Updated Meta-Analysis.

J Interv Cardiol 2021 22;2021:7099044. Epub 2021 Jul 22.

Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Objective: The previous meta-analysis has assessed that distal transradial access (dTRA) in anatomical snuffbox is safe and effective for coronary angiography and intervention and can reduce radial artery occlusion. However, since the publication of the previous meta-analysis, several observational studies have been added, so we performed an updated meta-analysis to include more eligible studies to compare distal transradial access in anatomical snuffbox with conventional transradial access (cTRA).

Method: Pubmed, Embase, and Cochrane Library databases were searched for relevant studies from the literature published until 5 January 2021 to evaluate catheterization/puncture failure, hematoma, radial artery spasm, radial artery occlusion (RAO), access time, fluoroscopy time, radiation dose area product, total procedure time, and hemostatic device removal time. The pooled odds ratio (OR), weighted mean difference (WMD), and standardized mean difference (SMD) with 95% confidence interval (95% CI) were calculated for dichotomous and continuous variables, respectively.

Results: A total of 9,054 patients from 14 studies were included in the meta-analysis, and we found no significant difference in catheterization/puncture failure (OR = 1.94, 95CI [0.97, 3.86], =0.06), hematoma (OR = 0.97, 95CI [0.55, 1.73], =0.926), radial artery spasm (OR = 0.76, 95CI [0.43, 1.36], =0.354), total procedure time (SMD = 0.23, 95CI [-0.21, 0.68], =0.308), or radiation dose area product (WMD = 216.88 Gy/cm, 95CI [-126.24, 560.00], =0.215), but dTRA had a lower incidence of RAO (OR = 0.39, 95CI [0.23, 0.66], < 0.001), shorter hemostatic device removal time (WMD = -66.62 min, 95CI [-76.68, -56.56], < 0.001), longer access time (SMD = 0.32, 95CI [0.08, 0.56], =0.008), and longer fluoroscopy time (SMD = 0.16, 95CI [-0.00, 0.33], =0.05) than cTRA.

Conclusion: Compared with the cTRA, the dTRA has a lower incidence of radial artery occlusion and shorter hemostatic device removal time, which is worthy of further evaluation in clinical practice.
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http://dx.doi.org/10.1155/2021/7099044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321763PMC
October 2021

MiR-26a-5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17.

Cell Biol Int 2021 Nov 23;45(11):2357-2367. Epub 2021 Aug 23.

Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, PR China.

Cardiac hypertrophy has been a high prevalence rate throughout the world. It has posed a big threat to public health due to limited therapeutic approaches. Previous studies showed that pathological cardiac hypertrophy was associated with autophagy, microRNAs (miRNA), and other signaling pathways, while the molecular mechanisms remain incompletely characterized. In this study, we used thoracic aortic constriction (TAC)-induced mice and angiotensin-II (Ang-II)-induced H9C2 cell line as cardiac hypertrophy model to investigate the role of miR-26a-5p in cardiac hypertrophy. We found that miR-26a-5p was downregulated in cardiac hypertrophy mice. Overexpression of miR-26a-5p by type 9 recombinant adeno-associated virus (rAAV9) reversed the heart hypertrophic manifestations. The phenotypes were also promoted by miR-26a-5p inhibitor in Ang-II-induced H9C2 cells. Through miRNA profile analysis and dual-luciferase reporter assay, ADAM17 was identified as a direct target of miR-26a-5p. Restored expression of ADAM17 disrupted the effect of miR-26a-5p on cardiac hypertrophy. To sum up, these results indicated that miR-26a-5p played an inhibitory role in cardiac hypertrophy and dysfunction via targeting ADAM17. The miR-26a-5p-ADAM17-cardiac hypertrophy axis provided special insight and a new molecular mechanism for a better understanding of cardiac hypertrophy disease, as well as the diagnostic and therapeutic practice.
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http://dx.doi.org/10.1002/cbin.11685DOI Listing
November 2021

Time-to-event prediction analysis of patients with chronic heart failure comorbid with atrial fibrillation: a LightGBM model.

BMC Cardiovasc Disord 2021 08 4;21(1):379. Epub 2021 Aug 4.

Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South Xinjian Road, Taiyuan, 030001, Shanxi Province, China.

Background: Chronic heart failure (CHF) comorbid with atrial fibrillation (AF) is a serious threat to human health and has become a major clinical burden. This prospective cohort study was performed to design a risk stratification system based on the light gradient boosting machine (LightGBM) model to accurately predict the 1- to 3-year all-cause mortality of patients with CHF comorbid with AF.

Methods: Electronic medical records of hospitalized patients with CHF comorbid with AF from January 2014 to April 2019 were collected. The data set was randomly divided into a training set and test set at a 3:1 ratio. In the training set, the synthetic minority over-sampling technique (SMOTE) algorithm and fivefold cross validation were used for LightGBM model training, and the model performance was performed on the test set and compared using the logistic regression method. The survival rate was presented on a Kaplan-Meier curve and compared by a log-rank test, and the hazard ratio was calculated by a Cox proportional hazard model.

Results: Of the included 1796 patients, the 1-, 2-, and 3-year cumulative mortality rates were 7.74%, 10.63%, and 12.43%, respectively. Compared with the logistic regression model, the LightGBM model showed better predictive performance, the area under the receiver operating characteristic curve for 1-, 2-, and 3-year all-cause mortality was 0.718 (95%CI, 0.710-0.727), 0.744(95%CI, 0.737-0.751), and 0.757 (95%CI, 0.751-0.763), respectively. The net reclassification index was 0.062 (95%CI, 0.044-0.079), 0.154 (95%CI, 0.138-0.172), and 0.148 (95%CI, 0.133-0.164), respectively. The differences between the two models were statistically significant (P < 0.05). Patients in the high-risk group had a significantly higher hazard of death than those in the low-risk group (hazard ratios: 12.68, 13.13, 14.82, P < 0.05).

Conclusion: Risk stratification based on the LightGBM model showed better discriminative ability than traditional model in predicting 1- to 3-year all-cause mortality of patients with CHF comorbid with AF. Individual patients' prognosis could also be obtained, and the subgroup of patients with a higher risk of mortality could be identified. It can help clinicians identify and manage high- and low-risk patients and carry out more targeted intervention measures to realize precision medicine and the optimal allocation of health care resources.
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http://dx.doi.org/10.1186/s12872-021-02188-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340471PMC
August 2021

Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis.

J Immunol Res 2021 8;2021:1815098. Epub 2021 Jul 8.

Center for Hypertension Care, Shanxi Medical University First Hospital, Taiyuan, Shanxi 030001, China.

Adiponectin is a small peptide secreted and a key component of the endocrine system and immune system. Although globular adiponectin protects myocardial ischemia/reperfusion-induced cardiomyocyte injury, the protective mechanisms remain largely unresolved. Using a neonatal rat ventricular myocyte hypoxia/reoxygenation model, we investigated the role of its potential mechanisms of necroptosis in globular adiponectin-mediated protection in hypoxia/reoxygenation-induced cardiomyocyte injury as compared to apoptosis. We found that globular adiponectin treatment attenuated cardiomyocyte injury as indicated by increased cell viability and reduced lactate dehydrogenase release following hypoxia/reoxygenation. Immunofluorescence staining and Western blotting demonstrated that both necroptosis and apoptosis were triggered by hypoxia/reoxygenation and diminished by globular adiponectin. Necrostatin-1 (RIP1-specific inhibitor) and Z-VAD-FMK (pan-caspase inhibitor) only mimicked the inhibition of necroptosis and apoptosis, respectively, by globular adiponectin in hypoxia/reoxygenation-treated cardiomyocytes. Globular adiponectin attenuated reactive oxygen species production, oxidative damage, and p38MAPK and NF-B signaling, all important for necroptosis and apoptosis. Collectively, our study suggests that globular adiponectin inhibits hypoxia/reoxygenation-induced necroptosis and apoptosis in cardiomyocytes probably by reducing oxidative stress and interrupting p38MAPK signaling.
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http://dx.doi.org/10.1155/2021/1815098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282401PMC
July 2021

Plasma ceramides and cardiovascular events in hypertensive patients at high cardiovascular risk.

Am J Hypertens 2021 Jul 7. Epub 2021 Jul 7.

Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China.

Background: Plasma ceramides (Cer) have been used to evaluate risk of cardiovascular events in patients with coronary heart disease. We investigated the performance of ceramides and ceramide score (CERT) in hypertensive patients at high cardiovascular risk.

Methods: Seven ceramides were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry in 920 essential hypertension patients at high cardiovascular risk, who visited Beijing Anzhen Hospital from September 2016 to September 2018 (median age: 49 years, 562 males). All patients were followed up for Major Adverse Cardiovascular Events (MACE), which included incident acute coronary syndrome, heart failure, stroke, and cardiovascular death.

Results: During mean 2.3-year follow-up, 71 patients experienced MACE. Cer(d18:1/16:0), Cer(d18:1/22:0) and Cer(d18:1/24:0)were highly significant in predicting MACE [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.76 (1.34-2.30), 0.55 (0.41-0.73) and 0.66 (0.47-0.92),, respectively]. Compared with traditional variables (comprising presence of cardiovascular risk factors, hypertension-mediated organ damage, and comorbidities), a novel CERT for hypertensive patients (CERT-HBP), composed of Cer(d18:1/16:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) and Cer(d18:1/22:0) respectively, increased the C-statistic from 0.751 (95%CI, 0.697-0.806) to 0.791 (95%CI, 0.737-0.845), p=0.010. Net reclassification improvement and integrated discrimination improvement were 0.648 (95%CI, 0.421-0.885, p<0.001) and 0.046 (95%CI, 0.025-0.068, p<0.001), respectively.

Conclusions: A ceramide-based CERT-HBP was established to evaluate risk of MACE in hypertensive patients at high cardiovascular risk. This may improve identification of high-risk patients requiring increased attention and aggressive therapy.
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http://dx.doi.org/10.1093/ajh/hpab105DOI Listing
July 2021

Improving Risk Identification of Adverse Outcomes in Chronic Heart Failure Using SMOTE+ENN and Machine Learning.

Risk Manag Healthc Policy 2021 8;14:2453-2463. Epub 2021 Jun 8.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People's Republic of China.

Purpose: This study sought to develop models with good identification for adverse outcomes in patients with heart failure (HF) and find strong factors that affect prognosis.

Patients And Methods: A total of 5004 qualifying cases were selected, among which 498 cases had adverse outcomes and 4506 cases were discharged after improvement. The study subjects were hospitalized patients diagnosed with HF from a regional cardiovascular hospital and the cardiology department of a medical university hospital in Shanxi Province of China between January 2014 and June 2019. Synthesizing minority oversampling technology combined with edited nearest neighbors (SMOTE+ENN) was used to pre-process unbalanced data. Traditional logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) were used to build risk identification models, and each model was repeated 100 times. Model discrimination and calibration were estimated using F1-score, the area under the receiver-operating characteristic curve (AUROC), and Brier score. The best performing of the five models was used to identify the risk of adverse outcomes and evaluate the influencing factors.

Results: The SME-XGBoost was the best performing model with means of F1-score (0.3673, 95% confidence interval [CI]: 0.3633-0.3712), AUC (0.8010, CI: 0.7974-0.8046), and Brier score (0.1769, CI: 0.1748-0.1789). Age, N-terminal pronatriuretic peptide, pulmonary disease, etc. were the most significant factors of adverse outcomes in patients with HF.

Conclusion: The combination of SMOTE+ENN and advanced machine learning methods effectively improved the discrimination efficacy of adverse outcomes in HF patients, accurately stratified patients at risk of adverse outcomes, and found the top factors of adverse outcomes. These models and factors emphasize the importance of health status data in determining adverse outcomes in patients with HF.
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http://dx.doi.org/10.2147/RMHP.S310295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206455PMC
June 2021

Trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016: a retrospective analysis of hospital quality monitoring system data.

J Hypertens 2021 Oct;39(10):2015-2021

Department of Cardiology, Peking University First Hospital, Beijing.

Background: Secondary hypertension has emerged as a major public health problem in China. Early diagnosis and treatment can significantly improve the clinical outcomes. However, data on the current cause composition in China are seldom reported.

Objective: To describe the trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016.

Methods: This was a retrospective analysis based on the national Hospital Quality Monitoring System (HQMS) database, which collects information from the front pages of in-hospital medical records. Hospitalized patients with secondary hypertension from 746 tertiary hospitals that consistently uploaded data to the HQMS from 2013 to 2016 were enrolled. All diagnoses were identified using International Classification of Diseases version 10 (ICD-10) diagnostic codes. Descriptive analyses were used to determine the proportions of secondary hypertension causes and changing trends over 4 years.

Result: The study collected data on 402 371 hospitalized patients with secondary hypertension from the HQMS during 2013-2016. Secondary hypertension caused by renal parenchymal disease ranked first and accounted for more than 50%. Obstructive sleep apnea syndrome (OSAS) followed closely with a rate of approximately 25%. Primary aldosteronism presented the highest proportion among all causes of endocrine hypertension. Regarding longitudinal changes over time, the rates of renal hypertension showed a significant downward trend from 2013 to 2016 (P < 0.001). In contrast, OSAS, endocrine hypertension, renal vascular disease, and aorta diseases maintained a significant upward trend from 2013 to 2016 (P < 0.001). The rates of these diseases in women with common secondary hypertension was higher than that of men, except in patients with OSAS (P < 0.001). In addition, renal parenchymal diseases and renal vascular diseases gradually decreased with age, whereas OSAS and aortic diseases gradually increased with age. The proportion of endocrine hypertension in the middle-aged group was higher than the other two age groups.

Conclusion: The study provides important information on the changing trends of cause rate of secondary hypertension modified by age and sex in China during 2013-2016. Renal parenchymal disease is still the most common cause of secondary hypertension with a decreasing trend, followed by OSAS with an increasing trend.
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http://dx.doi.org/10.1097/HJH.0000000000002891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452322PMC
October 2021

Oleanane-type saponins and prosapogenins from Albizia julibrissin and their cytotoxic activities.

Phytochemistry 2021 May 23;185:112674. Epub 2021 Mar 23.

State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China. Electronic address:

Two undescribed oleanane-type saponins, julibrosides K-L, along with three undescribed oleanane-type prosapogenins, julibrosides M-O, were isolated from the stem bark of Albizia julibrissin Durazz. and the mild alkaline hydrolysate of the total saponin, respectively. Their structures were established by extensive analysis of 1D and 2D NMR experiments (COSY, TOCSY, HSQC, HMBC, and HSQC-TOCSY) and mass spectrometry. Furthermore, the cytotoxic activities of the isolated compounds against BGC-823, A549, HCT-116, and HepG2 cell lines were evaluated, and julibroside L showed significant cytotoxic activities against the four cancer cell lines with IC values of 5.77, 4.80, 4.26, and 4.93 μM, respectively.
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http://dx.doi.org/10.1016/j.phytochem.2021.112674DOI Listing
May 2021

Assessment of chronic disease self-management in patients with chronic heart failure based on the MCID of patient-reported outcomes by the multilevel model.

BMC Cardiovasc Disord 2021 01 30;21(1):58. Epub 2021 Jan 30.

Department of Cardiology, The 1St Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, 030001, Shanxi Province, China.

Purpose: The minimal clinically important difference (MCID) of a patient-reported outcome (PRO) represents the threshold value of the change in the score for that PRO. It is deemed to have an important implication in clinical management. This study was performed to evaluate the clinical significance of chronic disease self-management (CDSM) for patients with chronic heart failure based on the MCID of the chronic heart failure-PRO measure (CHF-PROM).

Methods: A multicenter, prospective cohort study of 555 patients with heart failure were enrolled from July 2018. Advice of CDSM was provided in written form at discharge to all patients. Information regarding CHF-PROM and CDSM were collected during follow-up. Multilevel models were applied to dynamically evaluate the effects of CDSM for CHF-PROM scores, as well as its physical and psychological domains. MCID changes of the PRO were introduced and compared with β values of CDSM obtained from the multi-level models to further evaluate the clinical significance. The STROBE checklist is shown in Additional file 1.

Results: Scores for CHF-PROM improved significantly after discharge. The multilevel models showed that a regular schedule, avoidance of over-eating, a low-sodium diet and exercise increased scores on CHF-PROM. Compared with the MCID, avoidance of over-eating (12.39 vs. 9.75) and maintenance of a regular schedule often (10.98 vs. 9.75), and exercise almost every day (11.36 vs. 9.75) reached clinical significance for the overall summary. Avoidance of over-eating (5.88 vs. 4.79) and a regular schedule almost every day (4.96 vs. 4.79) reached clinical significance for the physical scores. Avoidance of over-eating half of the time (5.26 vs. 4.87) and a regular schedule almost every day (5.84 vs. 4.87) demonstrated clinical significance for the psychological scores.

Conclusions: This study observed an association of avoidance of over-eating and maintenance of a regular schedule with the improvement of CHF-PROM. It provides further evidence for management of heart failure.

Trial Registration: Current Prospective Trials NCT02878811; registered August 25, 2016; https://clinicaltrials.gov/ct2/show/NCT02878811?term=NCT02878811&draw=2&rank=1 .
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http://dx.doi.org/10.1186/s12872-021-01872-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847136PMC
January 2021

A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction.

Open Med (Wars) 2020 10;15(1):644-653. Epub 2020 Jul 10.

Department of Health Statistics, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, Shanxi Province 030001, People's Republic of China.

Purpose: A model for predicting the prognosis of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) is currently not available. This study aimed to develop an age-biomarker-clinical history prognostic index (ABC-PI) and validate it for the assessment of individual prognosis.

Patients And Methods: A total of 5,974 HFrEF patients were enrolled and 1,529 were included in this study after excluding missing values and loss to follow-up. Variables that significantly contributed to prediction of all-cause mortality were assessed by Cox regression and latent trait analysis (LTA) was used to validate discrimination of variables.

Results: After Cox regression, the following seven most significant variables were selected: age, N-terminal pro-B-type natriuretic peptide, renal dysfunction, left ventricular mass index, percutaneous coronary intervention, atrial fibrillation, and New York Heart Association (C-index: 0.801 ± 0.013). After verification by LTA, discrimination of these seven variables was proven. A nomogram was used to form the ABC-PI, and then the total score was set to 100 points. A lower score indicated a higher risk. After verification, the 3-year mortality rate was 34.7% in the high-risk group and only 2.6% in the low-risk group.

Conclusion: Our novel ABC-PI shows a good performance and does not require re-input in the original model. The ABC-PI can be used to effectively and practically predict the prognosis of HFrEF patients.
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http://dx.doi.org/10.1515/med-2020-0209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712124PMC
July 2020

A nomogram based on a patient-reported outcomes measure: predicting the risk of readmission for patients with chronic heart failure.

Health Qual Life Outcomes 2020 Aug 27;18(1):290. Epub 2020 Aug 27.

Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, Shanxi Province, China.

Background: Health-related quality of life, as evaluated by a patient-reported outcomes measure (PROM), is an important prognostic marker in patients with chronic heart failure. This study aimed to use PROM to establish an effective readmission nomogram for chronic heart failure.

Methods: Using a PROM as a measurement tool, we conducted a readmission nomogram for chronic heart failure on a prospective observational study comprising of 454 patients with chronic heart failure hospitalized between May 2017 to January 2020. A Concordance index and calibration curve were used to evaluate the discriminative ability and predictive accuracy of the nomogram. A bootstrap resampling method was used for internal validation of results.

Results: The median follow-up period in the study was 372 days. After a final COX regression analysis, the gender, income, health care, appetite-sleep, anxiety, depression, paranoia, support, and independence were identified and included in the nomogram. The nomogram showed moderate discrimination, with a concordance index of 0.737 (95% CI 0.673-0.800). The calibration curves for the probability of readmission for patients with chronic heart failure showed high consistency between the probability, as predicted, and the actual probability.

Conclusions: This model offers a platform to assess the risk of readmission for different populations with CHF and can assist clinicians with personalized treatment recommendations.
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http://dx.doi.org/10.1186/s12955-020-01534-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450976PMC
August 2020

Activation of microRNA-378a-3p biogenesis promotes hepatic secretion of VLDL and hyperlipidemia by modulating ApoB100-Sortilin1 axis.

Theranostics 2020 4;10(9):3952-3966. Epub 2020 Mar 4.

Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455.

: Hyperlipidemia is a major risk factor of atherosclerosis and cardiovascular diseases (CVD). As a standard-of-care approach for hyperlipidemia, statins only reduce the risk of coronary artery disease by 20-40%, underscoring the importance of identifying molecular pathways for the design of drugs against this disorder. Alterations in microRNA (miRNA) expression have been reported in patients with hyperlipidemia and CVD. This study was designed to determine the mechanism of dysregulated miR-378a-3p under the status of hyperlipidemia and evaluate how miR-378a-3p regulates hepatic secretion of VLDL. : Wild-type mice kept on a high fat diet were injected with miR-378a-3p inhibitor or a mini-circle expression system containing miR-378a precursor to study loss and gain-of functions of miR-378a-3p. Mice were treated with Triton WR1339 and S-methionine/cysteine to determine the effect of miR-378a-3p on hepatic secretion of VLDL. Database mining, luciferase assay, and ChIP (chromatin immunoprecipitation) were used to study the mechanism of dysregulated miR-378a-3p biogenesis. : miR-378a-3p expression is significantly increased in livers of hyperlipidemic mice. (sortilin 1) was identified as a direct target of miR-378a-3p. By inhibiting the function of sortilin 1 as a transmembrane trafficking receptor, miR-378a-3p stabilized ApoB100 and promoted ApoB100 secretion . Liver-specific expression of miR-378a-3p stabilized ApoB100 and facilitated hepatic secretion of VLDL, which subsequently increased levels of VLDL/LDL cholesterol as well as triglycerides. In contrast, antagonizing miR-378a-3p using its inhibitor increased hepatic expression of and reduced hepatic export of VLDL with its consequent effects of serum lipid levels. Additional knockdown of up-regulated in livers of mice offset the effects of miR-378a-3p inhibitor, suggesting that was indispensable for miR-378a-3p to promote secretion of VLDL and thereby high levels of circulating VLDL/LDL cholesterol and triglycerides. Furthermore, oncogenic E2F1 (E2F transcription factor 1) was identified as a transcriptional activator of miR-378a-3p. knockdown, through reducing miR-378a-3p, impaired secretion of VLDL and reduced levels of VLDL/LDL cholesterol and triglycerides. : This study defines a novel pathway of E2F1-miR-378a-3p-SORT1-ApoB100 that controls levels of circulating VLDL/LDL cholesterol and triglycerides by modulating degradation and secretion of ApoB100, and suggests the use of miR-378a-3p as a potential therapeutic target for dyslipidemia.
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http://dx.doi.org/10.7150/thno.39578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086368PMC
May 2021

LncRNA Tincr regulates PKCɛ expression in a miR-31-5p-dependent manner in cardiomyocyte hypertrophy.

Naunyn Schmiedebergs Arch Pharmacol 2020 12 10;393(12):2495-2506. Epub 2020 Mar 10.

The First Clinical Medical School, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan, 030001, Shanxi, People's Republic of China.

Cardiomyocyte hypertrophy is a fatal factor in heart disease resulting in heart failure and even mortality. Although many studies have been focusing on the pathogenesis of cardiomyocyte hypertrophy, the exact molecular mechanisms are still unexclusive. In this study, we first found that the expression level of lncRNA Tincr was significantly decreased in the myocardial tissues of TAC mouse models of cardiomyocyte hypertrophy, and this result was further confirmed in H9C2 cells, a widely used rat myoblast cell lines. More intriguingly, we demonstrated that the aberration of Tincr is essential to the pathogenesis of cardiomyocyte hypertrophy, indicated by the re-induction of Tincr improving the heart functions of hypertrophic mice. In mechanism, we identified miR-31-5p as a direct target of Tincr using a widely used online bioinformatics tool StarBase, and this result was further experimentally validated using dual-luciferase reporter assay and real-time PCR. Also, we identified PRKCE as a direct target of miR-31-5p, and loss function of miR-31-5p significantly blocks the positive regulatory effect of Tincr on PRKCE expression in H9C2 cells. The knockdown of Tincr resulted in increased cardiomyocyte size, and, however, inhibition of miR-31-5p or overexpression of PRKCE significantly reversed the increased cardiomyocyte size. Taken together, our study showed that a novel Tincr-miR-31-5p axis targeting PRKCE was involved in cardiomyocyte hypertrophy, indicating that it may provide potential therapy in cardiomyocyte hypertrophy.
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http://dx.doi.org/10.1007/s00210-020-01847-9DOI Listing
December 2020

Joint Sensor Selection and Power Allocation Algorithm for Multiple-Target Tracking of Unmanned Cluster based on Fuzzy Logic Reasoning.

Sensors (Basel) 2020 Mar 2;20(5). Epub 2020 Mar 2.

College of Electronic and Information Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.

The unmanned aerial vehicle (UAV) cluster is gradually attracting more attention, which takes advantage over a traditional single manned platform. Because the size of the UAV platform limits the transmitting power of its own radar, how to reduce the transmitting power while meeting the detection accuracy is necessary. Aim at multiple-target tracking (MTT), a joint radar node selection and power allocation algorithm for radar networks is proposed. The algorithm first uses fuzzy logic reasoning (FLR) to obtain the priority of targets to radars, and designs a radar clustering algorithm based on the priority to form several subradar networks. The radar clustering algorithm simplifies the problem of multiple-radar tracking multiple-target into several problems of multiple-radar tracking a single target, which avoids complex calculations caused by multiple variables in the objective function of joint radar node selection and power allocation model. Considering the uncertainty of the target RCS in practice, the chance-constraint programming (CCP) is used to balance power resource and tracking accuracy. Through the joint radar node selection and power allocation algorithm, the radar networks can use less power resource to achieve a given tracking performance, which is more suitable for working on drone platforms. Finally, the simulation proves the effectiveness of the algorithm.
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http://dx.doi.org/10.3390/s20051371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085682PMC
March 2020

Joint Adaptive Sampling Interval and Power Allocation for Maneuvering Target Tracking in a Multiple Opportunistic Array Radar System.

Sensors (Basel) 2020 Feb 12;20(4). Epub 2020 Feb 12.

College of Information Science and Engineering, Zaozhuang University, Zaozhuang 277160, China.

In this paper, a joint adaptive sampling interval and power allocation (JASIPA) scheme based on chance-constraint programming (CCP) is proposed for maneuvering target tracking (MTT) in a multiple opportunistic array radar (OAR) system. In order to conveniently predict the maneuvering target state of the next sampling instant, the best-fitting Gaussian (BFG) approximation is introduced and used to replace the multimodal prior target probability density function (PDF) at each time step. Since the mean and covariance of the BFG approximation can be computed by a recursive formula, we can utilize an existing Riccati-like recursion to accomplish effective resource allocation. The prior Cramér-Rao lower boundary (prior CRLB-like) is compared with the upper boundary of the desired tracking error range to determine the adaptive sampling interval, and the Bayesian CRLB-like (BCRLB-like) gives a criterion used for measuring power allocation. In addition, considering the randomness of target radar cross section (RCS), we adopt the CCP to package the deterministic resource management model, which minimizes the total transmitted power by effective resource allocation. Lastly, the stochastic simulation is embedded into a genetic algorithm (GA) to produce a hybrid intelligent optimization algorithm (HIOA) to solve the CCP optimization problem. Simulation results show that the global performance of the radar system can be improved effectively by the resource allocation scheme.
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http://dx.doi.org/10.3390/s20040981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070925PMC
February 2020

Analysis Of Re-Hospitalizations For Patients With Heart Failure Caused By Coronary Heart Disease: Data Of First Event And Recurrent Event.

Ther Clin Risk Manag 2019 14;15:1333-1341. Epub 2019 Nov 14.

Department of Cardiology, The 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province 030001, People's Republic of China.

Background: The re-hospitalization rate of patients with heart failure remains at a high level, and studies of the subject have focused mainly on event-time outcomes. In addition to using re-hospitalization data with the outcomes of the event-time-count, this study introduces the conditional frailty model, which could help obtain more reasonable results.

Materials And Methods: This prospective observational cohort study enrolled 1484 patients with heart failure caused by coronary heart disease. The outcomes of heart failure readmissions and the case report form data were collected. Based on the traditional Cox model with event-time outcomes, the mixed effects of a conditional frailty model were added to analyze the event-time-count longitudinal data.

Results: The Cox regression model showed that non-manual work, diastolic dysfunction, and better medical compensation increased the risk of heart failure readmission, whereas treatment with beta-blockers decreased the risk. The conditional frailty model further revealed that age, female sex, non-manual work, better medical compensation, longer QRS duration, and treatment with percutaneous coronary intervention increased the risk of heart failure readmission.

Conclusion: This study obtained more reliable, reasonable results based on longitudinal data and a mixed model. The results could provide more clinical epidemiological evidence for the management of heart failure.
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http://dx.doi.org/10.2147/TCRM.S218694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861516PMC
November 2019

MiR-195-5p Promotes Cardiomyocyte Hypertrophy by Targeting MFN2 and FBXW7.

Biomed Res Int 2019 25;2019:1580982. Epub 2019 Jun 25.

Shanxi Medical University, Taiyuan 030001, Shanxi, China.

Cardiac hypertrophy mainly predicts heart failure and is highly linked with sudden loss of lives. MicroRNAs (miRNAs) play essential roles in the development of cardiac hypertrophy through binding to corresponding mRNA targets. In this study, in order to investigate the roles of two mature forms of miRNA-195, miR-195-3p, and miR-195-5p, and models of cardiac hypertrophy were established by applying angiotensin II (Ang II) to H9c2 cardiomyocytes and infusing chronic Ang II to mice, respectively. We found that miR-195-5p was evidently equally upregulated in the and studies of cardiac hypertrophy induced by Ang II. High expressed miR-195-5p could adequately promote hypertrophy, whereas the suppression of miR-195-5p prevented hypertrophy of H9c2 cardiomyocytes under Ang II treatment. Furthermore, the luciferase reporter system demonstrated that MFN2 and FBWX7 were target genes of miR-195-5p, which negatively regulated the expression of these two genes in H9c2 cells. By contrast, in both models, expression of miR-195-3p was only slightly changed without statistical significance. In addition, we observed a trend towards decreased expression of hypertrophic markers by overexpressing miR-195-3p in AngII-treated H9c2 cardiomyocytes . Taken together, our study indicates that miR-195-5p promotes cardiac hypertrophy via targeting MFN2 and FBXW7 and may provide promising therapeutic strategies for interfering cardiac hypertrophy.
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http://dx.doi.org/10.1155/2019/1580982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614993PMC
December 2019

Visit-to-visit variability in blood pressure and the development of chronic kidney disease in treated general hypertensive patients.

Nephrol Dial Transplant 2020 10;35(10):1739-1746

Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of chronic kidney disease (CKD) in general treated hypertensive patients were limited. We aimed to evaluate the relation of VVV in BP with the development of CKD, and examine any possible effect modifiers in hypertensive patients without prior cardiovascular diseases (CVDs) or CKD.

Methods: This is a post hoc analysis of the Renal Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 10 051 hypertensives without CVD and CKD and with at least six visits of BP measurements from randomization to the 24-month visit were included. The main VVV in BP was expressed as standard deviation (SD). The primary outcome was the development of CKD, defined as a decrease in estimated glomerular filtration rate ≥30% and to a level of <60 mL/min/1.73 m2, or end-stage renal disease.

Results: The median treatment duration was 4.4 years. After multivariable adjustment, including baseline systolic blood pressure (SBP) and mean SBP during the first 2-year treatment period, there was a significantly positive relationship of SD of SBP with the risk of CKD development (per SD increment; odds ratio, 1.27; 95% confidence interval: 1.10-1.46). The results were similar for coefficient of variation (CV) of SBP. Results across various subgroups, including age, sex, SBP at baseline, treatment compliance, concomitant antihypertensive medications and mean SBP during the first 24-month treatment period, were consistent.

Conclusions: SBP variability, irrespective of mean BP level, was significantly associated with the development of CKD in general treated hypertensive patients.
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http://dx.doi.org/10.1093/ndt/gfz093DOI Listing
October 2020

Exercise ameliorates the FGF21-adiponectin axis impairment in diet-induced obese mice.

Endocr Connect 2019 May;8(5):596-604

Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sports University, Guangzhou, China.

Objective: The protective effects of exercise against glucose dysmetabolism have been generally reported. However, the mechanism by which exercise improves glucose homeostasis remains poorly understood. The FGF21-adiponectin axis participates in the regulation of glucose metabolism. Elevated levels of FGF21 and decreased levels of adiponectin in obesity indicate FGF21-adiponectin axis dysfunction. Hence, we investigated whether exercise could improve the FGF21-adiponectin axis impairment and ameliorate disturbed glucose metabolism in diet-induced obese mice.

Methods: Eight-week-old C57BL/6J mice were randomly assigned to three groups: low-fat diet control group, high-fat diet group and high-fat diet plus exercise group. Glucose metabolic parameters, the ability of FGF21 to induce adiponectin, FGF21 receptors and co-receptor levels and adipose tissue inflammation were evaluated after 12 weeks of intervention.

Results: Exercise training led to reduced levels of fasting blood glucose and insulin, improved glucose tolerance and better insulin sensitivity in high-fat diet-induced obese mice. Although serum FGF21 levels were not significantly changed, both total and high-molecular-weight adiponectin concentrations were markedly enhanced by exercise. Importantly, exercise protected against high-fat diet-induced impaired ability of FGF21 to stimulate adiponectin secretion. FGF21 co-receptor, β-klotho, as well as receptors, FGFR1 and FGFR2, were upregulated by exercise. We also found that exercise inhibited adipose tissue inflammation, which may contribute to the improvement in the FGF21-adiponectin axis impairment.

Conclusions: Our data indicate exercise protects against high-fat diet-induced FGF21-adiponectin axis impairment, and may thereby exert beneficial effects on glucose metabolism.
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http://dx.doi.org/10.1530/EC-19-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510890PMC
May 2019

MicroRNA-148b-3p is involved in regulating hypoxia/reoxygenation-induced injury of cardiomyocytes in vitro through modulating SIRT7/p53 signaling.

Chem Biol Interact 2018 Dec 9;296:211-219. Epub 2018 Oct 9.

Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.

Accumulating evidence has suggested that microRNAs (miRNAs) are emerging as critical regulators in myocardial ischemia/reperfusion injury. miR-148b-3p has been reported to regulate cell apoptosis of various cell types. However, whether miR-148b-3p is involved in regulating cardiomyocyte apoptosis in myocardial ischemia/reperfusion injury remains unknown. In this study, we aimed to investigate the potential role and molecular mechanism of miR-148b-3p in regulating cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury in vitro, a cellular model of myocardial ischemia/reperfusion injury. We found that miR-148b-3p expression was significantly up-regulated in response to H/R treatment in cardiomyocytes. Functional experiments showed that miR-148b-3p overexpression significantly decreased the viability, increased LDH release and promoted the apoptosis of H/R-treated cardiomyocytes. In contrast, miR-148b-3p inhibition improved the viability, decreased LDH release and reduced the apoptosis of H/R-treated cardiomyocytes, showing a protective effect against H/R-induced injury. Bioinformatics analysis predicted that Sirtuin7 (SIRT7), a critical stress survival gene of cardiomyocytes, was a potential target gene of miR-148b-3p, which was then validated by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Moreover, our results showed that miR-148b-3p regulated the acetylation of the p53 protein and modulated p53-mediated pro-apoptotic signaling through targeting SIRT7. Notably, the silencing of SIRT7 significantly abrogated miR-148b-3p inhibition-mediated cardio-protective effects, while SIRT7 overexpression rescued miR-148b-3p-induced cell apoptosis in cardiomyocytes with H/R treatment. Overall, our results indicate that miR-148b-3p contributes to the regulation of H/R-induced cardiomyocyte apoptosis in vitro through targeting SIRT7 and modulating p53-mediated pro-apoptotic signaling.
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http://dx.doi.org/10.1016/j.cbi.2018.10.003DOI Listing
December 2018

Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats.

Clin Exp Hypertens 2019 9;41(4):312-322. Epub 2018 Jul 9.

a Department of Cardiology , The First Hospital of Shanxi Medical University , PR China.

Recent evidence suggests that elevated plasma levels of Trimethylamine-N-oxide (TMAO) can prolong the duration of elevated blood pressure in rats. The purpose of this study was to investigate the plasma TMAO level in Spontaneously Hypertensive Rats (SHR) and to explore the possible relationship between TMAO and aquaporin-2 (AQP-2) in the formation of hypertension. Twelve-week-old, male Spontaneously Hypertensive rats (SHR, n = 40) and Wistar-Kyoto rats (WKY, n = 40) were accordingly grouped into SHR group and WKY group. Each group was divided randomly into four subgroups: Untreated group, TMAO group, TMAO+Tolvaptan (TMAO+TVP) group, and TVP group, respectively. Systolic blood pressure (SBP), plasma TMAO, plasma osmolality (POsm), plasma vasopressin (PAVP), and plasma AQP-2 (PAQP-2) concentration were measured, and the expression of AQP-2 in kidney medulla was detected by RT-PCR and Western blot. At 14 weeks, rats in SHR TMAO group were shown the increased plasma TMAO, POsm, PAVP, and PAQP-2 levels, while those rats in SHR TMAO+TVP group were shown the decreased plasma TMAO, POsm, and PAQP-2 levels, but an even higher PAVP (due to the blockage of TVP to V2 receptor). These findings indicate that an increase of plasma TMAO levels in SHR leads to a higher plasma osmotic pressure, triggers the regulation of the TMAO-AVP-AQP-2 axis in SHR, elicits the greater water reabsorption, and eventually leads to hypertension.
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http://dx.doi.org/10.1080/10641963.2018.1481420DOI Listing
May 2019

CHF-PROM: validation of a patient-reported outcome measure for patients with chronic heart failure.

Health Qual Life Outcomes 2018 Mar 20;16(1):51. Epub 2018 Mar 20.

Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, Shanxi Province, 030001, China.

Background: Due to a lack of an appropriate disease-specific patient-reported outcome (PRO) instrument for chronic heart failure including its social support and treatment aspects in China, this study was performed to develop a patient-reported outcome measure (PROM) for patients with chronic heart failure and evaluate its reliability, validity, and feasibility.

Methods: According to the standard PROM guidelines established by the Food and Drug Administration, an item pool was formed by reviewing a large amount of relevant literature and interviewing patients with chronic heart failure about their main symptoms. Thus, the primary scale was created after adjusting the items and language with the help of patients and experts in the field. Next, 155 patients from 8 hospitals in different districts were recruited for a pilot survey using questionnaires containing these items. The patients' responses were analyzed using the classical test theory and item response theory to select high-quality items and determine the subdomains of the scale. This was followed by a formal investigation in the same eight hospitals. In total, 360 patients and 100 healthy subjects were included to evaluate the reliability, validity, and feasibility of the items. Through this process, the final scale was established.

Results: The final scale comprised 12 subdomains with 57 items related to physical, psychological, social, and therapeutic areas. The data analysis results of the formal investigation showed that the PROM for chronic heart failure had good reliability, validity, and feasibility. Reliability was verified by Cronbach's alpha coefficient, which was 0.913 for the total scale, 0.903 for the physical domain, 0.941 for the psychological domain, 0.827 for the social domain, and 0.839 for the therapeutic domain. The construct validity results met the relative criteria of confirmatory factor analysis. Discriminant validity was represented by score comparisons of nine subdomains. The response rate and the effective rate of return of the CHF-PROM were 98.94% and 98.92%, respectively.

Conclusions: The final scale coincides with the theoretical framework and better reflects the overall quality of life of patients with chronic heart failure. This scale can be used as a valid instrument to evaluate clinical treatment and clinical trials of chronic heart failure.
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http://dx.doi.org/10.1186/s12955-018-0874-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859646PMC
March 2018

Cytotoxic oleanane triterpenoid saponins from Albizia julibrissin.

Fitoterapia 2017 Sep 29;121:183-193. Epub 2017 Jul 29.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, People's Republic of China. Electronic address:

Bioassay-guided fractionation of the ethanolic extract of the stem bark of Albizia julibrissin led to the isolation of ten new oleanane-type triterpenoid saponins, julibrosides J-J (1-10), along with six known analogues (11-16). In addition, 11 prosapogenins (17-27) were prepared by mild or strong alkaline hydrolysis of the total saponin. The structures of 1-27 were determined by spectroscopic and chemical means, and their cytotoxicities against four human cancer cell lines, BGC-823, A549, HCT-116, and HepG2 were evaluated. Compounds 5-16 exhibited significant inhibitory activity with IC values ranging from 2.59 to 9.30μM, and 8 turned out to be the most active compound with all IC values <5μM. A preliminary structure-activity relationship of these saponins clearly indicated that the outer monoterpenoid moiety (MT') is a crucial substituent for cytotoxicity, and the linkage sites of the MT' unit greatly influenced the activity. It could also be inferred that the existence of 16-OH of the aglycone almost has no effect on cytotoxicity and the N-acetyl-glucosamine moiety at C-3 seems to enhance activity.
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http://dx.doi.org/10.1016/j.fitote.2017.07.015DOI Listing
September 2017

Role of PKA in the process of neonatal cardiomyocyte hypertrophy induced by urotensin II.

Int J Mol Med 2017 Aug 22;40(2):499-504. Epub 2017 Jun 22.

Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

The model of urotensin II (UII)-induced cardiomyocyte hypertrophy has been widely used in studies on hypertrophy. However, the molecular mechanisms responsible for UII-induced cardiomyocyte hypertrophy have not yet been fully elucidated. It has been demonstrated that cardiomyocyte hypertrophy induced by UII is associated with changes in the intracellular Ca2+ concentration. In the present study, we investigated whether the cAMP-dependent protein kinase A (PKA)‑mediated upregulation of the phosphorylation levels of phospholamban (PLN) at Ser16 contributes to UII-induced cardiomyocyte hypertrophy. After primary cultures of neonatal rat cardiomyocytes were exposed to UII for 48 h, cell size, protein/DNA contents and intracellular Ca2+ levels were detected. Western blot analysis was used to quantify the phosphorylated and total forms of PKA, PLN and the total amount of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)2a. UII increased the cell size, the protein/DNA ratio and the intracellular Ca2+ levels, consistent with the characteristics of hypertrophic response. In addition, exposure to UII upregulated the phosphorylation levels of PKA, and the expression levels of its downstream proteins, PLN and SERCA2a. However, treatment with PKA inhibitor (KT-5720) reversed all these effects of UII. On the whole, our results suggest that UII induces cardiomyocyte hypertrophy through the PKA-mediated upregulation of PLN phosphorylation at Ser16, which provides a new experimental foundation for the prevention and/or treatment of cardiac hypertrophy.
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http://dx.doi.org/10.3892/ijmm.2017.3038DOI Listing
August 2017

Inhibition of leukotriene B4 receptor 1 attenuates lipopolysaccharide-induced cardiac dysfunction: role of AMPK-regulated mitochondrial function.

Sci Rep 2017 03 14;7:44352. Epub 2017 Mar 14.

Department of Cardiology, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, China.

Leukotriene B4 (LTB4)-mediated leukocyte recruitment and inflammatory cytokine production make crucial contributions to chronic inflammation and sepsis; however, the role of LTB4 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains unclear. Therefore, the present study addressed this issue using an LTB4 receptor 1 (BLT1) inhibitor. Administration of LPS to mice resulted in decreased cardiovascular function. Inhibition of LTB4/BLT1 with the BLT1 inhibitor U75302 significantly improved survival and attenuated the LPS-induced acute cardiac dysfunction. During LPS challenge, the phosphorylated AMPK/ACC signaling pathway was slightly activated, and this effect was enhanced by U75302. Additionally, pNF-κB, Bax and cleaved caspase-3 were upregulated by LPS, and Bcl-2, IκB-α, mitochondrial complex I, complex II, and OPA1 were downregulated; however, these effects were reversed by U75302. The results indicated that the BLT1 antagonist suppressed cardiac apoptosis, inflammation, and mitochondrial impairment. Furthermore, the protection provided by the BLT1 inhibitor against LPS-induced cardiac dysfunction was significantly reversed by the AMPK inhibitor Compound C. In conclusion, inhibiting the LTB4/BLT1 signaling pathway via AMPK activation is a potential treatment strategy for septic cardiac dysfunction because it efficiently attenuates cardiac apoptosis, which may occur via the inhibition of inflammation and mitochondrial dysfunction.
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http://dx.doi.org/10.1038/srep44352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349523PMC
March 2017

MicroRNA-223-5p and -3p Cooperatively Suppress Necroptosis in Ischemic/Reperfused Hearts.

J Biol Chem 2016 09 8;291(38):20247-59. Epub 2016 Aug 8.

Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267,

Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced necrosis can be controlled by multiple genes. In this study, we observed that both strands (5p and 3p) of miR-223 were remarkably dysregulated in mouse hearts upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited better recovery of contractile performance over reperfusion period and lesser degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL necroptotic pathway and inflammatory response were suppressed in transgenic hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R-triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically, we identified two critical cell death receptors, TNFR1 and DR6, as direct targets of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and IκB kinase α, two important mediators known to be involved in I/R-induced inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for the treatment of ischemic heart disease.
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http://dx.doi.org/10.1074/jbc.M116.732735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025706PMC
September 2016
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