Publications by authors named "Guosheng Fu"

122 Publications

Mitochondria-associated membrane-modulated Ca transfer: A potential treatment target in cardiac ischemia reperfusion injury and heart failure.

Life Sci 2021 Apr 14;278:119511. Epub 2021 Apr 14.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, China. Electronic address:

Effective Ca dependent mitochondrial energy supply is imperative for proper cardiac contractile activity, while disruption of Ca homeostasis participates in the pathogenesis of multiple human diseases. This phenomenon is particularly prominent in cardiac ischemia and reperfusion (I/R) and heart failure, both of which require strict clinical intervention. The interface between endoplasmic reticula (ER) and mitochondria, designated the mitochondria-associated membrane (MAM), is now regarded as a crucial mediator of Ca transportation. Thus, interventions targeting this physical and functional coupling between mitochondria and the ER are highly desirable. Increasing evidence supports the notion that restoration, and maintenance, of the physiological contact between these two organelles can improve mitochondrial function, while inhibiting cell death, thereby sufficiently ameliorating I/R injury and heart failure development. A better understanding regarding the underlying mechanism of MAM-mediated transport will pave the way for identification of novel treatment approaches for heart disease. Therefore, in this review, we summarize the crucial functions and potential mechanisms of MAMs in the pathogenesis of I/R and heart failure.
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http://dx.doi.org/10.1016/j.lfs.2021.119511DOI Listing
April 2021

Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation.

Aging (Albany NY) 2021 Apr 6;13(8):12016-12030. Epub 2021 Apr 6.

Department of Cardiology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, HangZhou, China.

Background: Despite growing evidence indicating that patients with inflammatory bowel disease (IBD) have an increased risk of atrial fibrillation (AF), owing to the potential biases of confounding effects and reverse causation, the specific relationship between IBD and AF remains controversial. The aim of this study is to determine whether there is a causal effect of IBD on AF.

Methods: A two-sample Mendelian randomization (MR) study was performed to evaluate the causal effect of IBD on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and traits of interest were obtained from independent consortia with European populations. The dataset of IBD was acquired from genome-wide association studies (GWAS), including more than 75,000 cases and controls. A GWAS with 60,620 AF cases and 970,216 controls was used to identify genetic variation underlying AF. The causal effect was estimated using the multiplicative random effects inverse-variance weighted method (IVW), followed by sensitivity analysis.

Results: Using 81 SNPs, there was no evidence to suggest an association between genetically predicted IBD and risk of AF with multiplicative random-effects IVW MR analysis (odds ratio = 1.0000, 95% confidence interval: 0.9994 1.0005, p = 0.88).

Conclusion: As opposed to current assumptions, no substantial evidence was found to support a causal role of IBD in the development of AF.
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http://dx.doi.org/10.18632/aging.202906DOI Listing
April 2021

Feasibility and safety of both His bundle pacing and left bundle branch area pacing in atrial fibrillation patients: intermediate term follow-up.

J Interv Card Electrophysiol 2021 Mar 15. Epub 2021 Mar 15.

Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qingchun East Road, Hangzhou, 310016, Zhejiang, People's Republic of China.

Purpose: His bundle pacing (HBP) improves heart failure (HF) in atrial fibrillation (AF) pacing-dependent patients with a potential for a progressively increased threshold. HBP with right ventricular pacing (RVP) as a backup is always the preferred choice; however, RVP may induce HF. His Purkinje system pacing (HPSP) includes HBP and left bundle branch area pacing (LBBAP). LBBAP maintains left ventricular synchrony but has not been proven to be safe over the long term. We assessed the feasibility and safety of both HBP and LBBAP in AF pacing-dependent patients and compared the parameters of both leads at baseline and at the 6-month follow-up.

Methods: A total of 16 AF patients in our center, who successfully attempted both HBP and LBBAP, were prospectively enrolled unless only one of these treatment statuses was attained. The electrocardiogram characteristics, leading parameters, echocardiography results, and clinical outcomes were assessed.

Results: Thirteen out of 16 patients achieved both HBP and LBBAP successfully in the same AF pacing-dependent patients. In symptomatic HF patients with preserved left ventricular ejection fraction (LVEF) (n = 10), the left ventricular end-diastolic diameter (LVEDD) was reduced from 51.8 ± 4.4 to 48.3 ± 3.1 mm (p = 0.01) with the use of diuretics, either reduced or stopped (n = 7). During the follow-up, one patient in the group without HF had an increased HBP threshold and developed HF symptoms. His HF symptoms disappeared when switched into LBBAP mode. Another patient in the group with HF got his LVEF elevated by HBP for 3 months by utilizing left bundle branch block(LBBB)correction and continued to increase when switched into LBBAP for another 3 months due to an increased HBP correction threshold. The average unipolar pacing threshold of LBBAP was lower than that of HBP. No perforation or dislodgement occurred in our study.

Conclusion: Both HBP and LBBAP could be attempted successfully in the same AF patients when one of the two modes could be adopted and switched according to the clinical feasibility. Compared with HBP, LBBAP yielded better and more stable parameters but showed comparable effects during the 6-month follow-up.
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http://dx.doi.org/10.1007/s10840-021-00964-6DOI Listing
March 2021

Effects of salvianolate on microcirculatory disturbance in patients with stable coronary heart disease: study protocol for a randomized controlled trial.

Trials 2021 Mar 8;22(1):192. Epub 2021 Mar 8.

Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People's Republic of China.

Background: Obstruction of coronary microcirculation can lead to myocardial ischemia and poor prognosis. Salvianolate exerts cardiovascular protection at cellular levels. However, no studies have confirmed the effect of salvianolate on stable coronary heart disease (CHD) with high fractional flow reserve (FFR) and myocardial microcirculatory disturbances.

Methods/design: This study will enroll 78 patients who have stable coronary disease with 50 to 70% stenosis in major coronary arteries and whose FFR > 0.80 and index of microcirculatory resistance (IMR) > 25. Patients will be randomly divided into the salvianolate group or the placebo group. After above evaluations, salvianolate 200 mg will be intravenously dripped immediately for the next 30 min and subsequent 7 days in the salvianolate group, and matching 0.9% normal saline will be arranged in the placebo group. IMR will be reevaluated in immediate phase after first 30 min of salvianolate or placebo treatment. The primary end point will be the IMR change in this phase, and the secondary end points will be the total ischemic burden assessed by the Seattle angina scale, quality of life scale, Holter electrocardiography, and 6-min walk test after 7 days before discharge.

Discussion: This study will firstly clarify the improvement effect of salvianolate on coronary microcirculation and provide an effective treatment method for stable CHD patients with high FFR and myocardial microcirculatory disturbance.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800018772 . Registered on 9 October 2018 and updated on 2 March 2020.
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http://dx.doi.org/10.1186/s13063-021-05099-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938457PMC
March 2021

Safety and Efficacy of Perioperative Use of Evolocumab in Myocardial Infarction Patients: Study Protocol for a Multicentre Randomized Controlled Trial.

Adv Ther 2021 04 27;38(4):1801-1810. Epub 2021 Feb 27.

Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People's Republic of China.

Introduction: The SECURE-PCI study supports a perioperative loading dose of statins, although whether an intensive lipid-lowering strategy prior to percutaneous coronary intervention further benefits acute coronary syndrome patients remains controversial. Evolocumab, a proprotein-converting enzyme subtilisin/kexin type 9 (PCSK9) inhibitor, acts more quickly and effectively than statins and reduces the risk of cardiovascular events in post-myocardial infarction (MI) patients. Nonetheless, whether it can be safely used in perioperative MI patients and whether perioperative application can benefit patients are still unknown. This study aims to evaluate the safety and efficacy of this treatment regimen.

Methods: A multicentre, prospective, randomized, controlled superiority trial will be conducted in 530 statin-naïve MI patients. All eligible patients will be randomized to the evolocumab group (140 mg subcutaneously injected once before revascularization + 14 days after the first dose) or the control group (no evolocumab injection). Evolocumab will then be administered depending on the patient's lipid profile. Both groups will be treated simultaneously with standardized secondary preventive medications. The primary end points are major adverse cardiovascular events (a composite of death, recurrent MI, unanticipated revascularization, stroke and any rehospitalization for ischaemic causes) within 12 months. The secondary end point is post-infarction angina after pain relief. The safety end points include myopathy, impaired liver or renal function, and other adverse events during the follow-up period.

Outcomes: This is the first trial to evaluate the safety and efficacy of evolocumab pre-treatment on prognosis in MI patients. Perioperative evolocumab injection may be a new, safe way to improve prognosis.

Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ; ChiCTR1900024526). Registered on 13 July 2019 and updated on 31 May 2020. The study is currently recruiting patients.
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http://dx.doi.org/10.1007/s12325-021-01662-5DOI Listing
April 2021

Expression of farnesyl pyrophosphate synthase is increased in diabetic cardiomyopathy.

Cell Biol Int 2021 Feb 17. Epub 2021 Feb 17.

Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.

Farnesyl pyrophosphate synthase (FPPS)-catalyzed isoprenoid intermediates are involved in diabetic cardiomyopathy. This study investigated the specific role of FPPS in the development of diabetic cardiomyopathy. We demonstrated that FPPS expression was elevated in both in vivo and in vitro models of diabetic cardiomyopathy. FPPS inhibition decreased the expression of proteins related to cardiac fibrosis and cardiomyocytic hypertrophy, including collagen I, collagen III, connective tissue growth factor, natriuretic factor, brain natriuretic peptide, and β-myosin heavy chain. Furthermore, FPPS inhibition and knockdown prevented phosphorylated c-Jun N-terminal kinase 1/2 (JNK1/2) activation in vitro. In addition, a JNK1/2 inhibitor downregulated high-glucose-induced responses to diabetic cardiomyopathy. Finally, immunofluorescence revealed that cardiomyocytic size was elevated by high glucose and was decreased by zoledronate, small-interfering farnesyl pyrophosphate synthase (siFPPS), and a JNK1/2 inhibitor. Taken together, our findings indicate that FPPS and JNK1/2 may be part of a signaling pathway that plays an important role in diabetic cardiomyopathy.
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http://dx.doi.org/10.1002/cbin.11573DOI Listing
February 2021

Shexiang Tongxin dropping pill protects against sodium laurate-induced coronary microcirculatory dysfunction in rats.

J Tradit Chin Med 2021 02;41(1):89-97

Department of Cardiology, Shaoxing Hospital, Zhejiang University school of medicine, Shaoxing 312000, China.

Objective: To investigate the protective effects of Shexiang Tongxin dropping pill (, STDP) in a rat model of coronary microcirculatory dysfunction (CMD).

Methods: Sprague-Dawley rats were allocated randomly into four groups: sham, CMD model, STDP, and nicorandil. After 4 weeks of treatment, CMD was induced by injection of sodium laurate (0.2 mL, 2 g/L) into the left ventricle while obstructing the ascending aorta. Rats in the sham group underwent an identical surgical procedure but were administered physiological (0.9% ) saline (0.2 mL). Twenty-four hours after surgery, blood samples were collected for biochemical analyses and enzyme-linked immunosorbent assays. Heart tissues were removed for histopathology staining; apoptosis and inflammatory cytokines were examined by Western blotting.

Results: The STDP group had a lower level of creatine kinase-myocardial band, lactate dehydrogenase, and cardiac troponin-I than that in the CMD model group. Infiltration of inflammatory cells, myocardial ischaemia, and microthrombosis were relieved in the STDP group compared with CMD model group. Levels of endothelin-1, nuclear factor-kappa B, tumour necrosis factor-α, interleukin-6, interleukin-1β, malondialdehyde, B-cell lymphoma (Bcl)-2-associated X protein, and caspase-3 were lower, and levels of nitric oxide, Bcl-2, and superoxide dismutase were higher, in the STDP group in comparison with the CMD model group.

Conclusion: STDP pretreatment improved the CMD induced by sodium laurate via anti-inflammatory, anti-apoptosis, and anti-oxidant mechanisms.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.01.011DOI Listing
February 2021

Diagnostic accuracy of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) estimated retrospectively by conventional radiation saving X-ray angiography.

Int J Cardiovasc Imaging 2021 May 16;37(5):1491-1501. Epub 2021 Jan 16.

Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UK.

Background: Angiography derived FFR reveals good performance in assessing intermediate coronary stenosis. However, its performance under contemporary low X-ray frame and pulse rate settings is unknown. We aim to validate the feasibility and performance of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) under such angiograms.

Methods: This was an observational, retrospective, single center cohort study. 134 vessels in 102 patients, with angiograms acquired under 7.5fps and 7pps mode, were enrolled. QFR (fQFR and cQFR) and vFFR were validated with FFR as the gold standard. A conventional manual and a newly developed algorithmic exclusion method (M and A group) were both evaluated for identification of poor-quality angiograms.

Results: Good agreement between QFR/vFFR and FFR were observed in both M and A group, except for vFFR in the M group. The correlation coefficients between fQFR/cQFR/vFFR and FFR were 0.6242, 0.5888, 0.4089 in the M group, with r significantly lower than r (p = 0.0303), and 0.7055, 0.6793, 0.5664 in the A group, respectively. AUCs of detecting lesions with FFR ≤ 0.80 were 0.852 (95% CI 0.722-0.913), 0.858 (95% CI 0.778-0.917), 0.682 (95% CI 0.586-0.768), for fQFR/cQFR/vFFR in the M group, while vFFR performed poorer than fQFR (p = 0.0063) and cQFR (p = 0.0054). AUCs were 0.898 (95% CI 0.811-0.945), 0.892 (95% CI 0.803-0.949), 0.843 (95% CI 0.746-0.914) for fQFR/cQFR/vFFR in the A group. AUC was significantly higher in the A group than that in the M group (p = 0.0399).

Conclusions: QFR/vFFR assessment is feasible under 7.5fps and 7pps angiography, where cQFR showed no advantage compared to fQFR. Our newly developed algorithmic exclusion method could be a better method of selecting angiograms with adequate quality for angiography derived FFR assessment.
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http://dx.doi.org/10.1007/s10554-020-02133-8DOI Listing
May 2021

Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima.

Cardiovasc Drugs Ther 2021 Jan 4. Epub 2021 Jan 4.

Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China.

Purpose: Anti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro.

Methods: We applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs).

Results: Low-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway.

Conclusion: Low-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.
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http://dx.doi.org/10.1007/s10557-020-07121-7DOI Listing
January 2021

Electrophysiological Insights into Three Modalities of Left Bundle Branch Area Pacing in Patients Indicated for Pacing Therapy.

Int Heart J 2021 Jan 26;62(1):78-86. Epub 2020 Dec 26.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University of Medicine.

Left bundle branch pacing (LBBP) has been adopted as a new pacing therapy whether in routine pacing or patients with heart failure, but the criteria for a completely captured LBBP are too complicated and have a low success rate in routine clinical practice.Consecutive patients with pacing therapy indications were enrolled. Left bundle branch area pacing (LBBAP) was conducted, and the presence of LBB potential, paced QRS duration, stimulus to left ventricular activation time (Stim-LVAT), and LBB potential to left ventricular activation time (LBB po-LVAT) were determined and utilized to characterize LBBAP modalities. Pacing parameters and safety were assessed at 6-month follow-up. LBBAP succeeded in 95.6% of patients (103/106) who completed the 6-month follow-up. Complete LBBP was achieved in 21 (20%) patients, characterized with a short Stim-LVAT equal to LBB po-LVAT. Incomplete LBBP was achieved in 58 (56%) patients with a short Stim-LVAT equal to LBB po-LVAT at a high pacing output and a relatively longer Stim-LVAT at a low pacing output. Deep septal pacing (DSP) characterized with no LBB potential and a longer Stim-LVAT (83.3 ± 7.7 ms) than that in LBBP (71.37 ± 7.1 ms, P < 0.01 versus DSP) was observed in 24 (23%) patients. Complete LBBP had a longer total procedure time and longer fluoroscopic time than the other two groups.This study describes the similarities and differences in electrophysiological characteristics and the possible mechanisms of the different types of LBBAP, classified into 3 modalities in routine clinical practice, each with narrow paced QRS duration and stable parameters, indicating LBBAP can be a near-physiological pacing modality.
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http://dx.doi.org/10.1536/ihj.20-490DOI Listing
January 2021

Weighted gene co-expression network analysis identified underlying hub genes and mechanisms in the occurrence and development of viral myocarditis.

Ann Transl Med 2020 Nov;8(21):1348

Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Myocarditis is an inflammatory myocardial disease, which may lead to heart failure and sudden death. Despite extensive research into the pathogenesis of myocarditis, effective treatments for this condition remain elusive. This study aimed to explore the potential pathogenesis and hub genes for viral myocarditis.

Methods: A weighted gene co-expression network analysis (WGCNA) was performed based on the gene expression profiles derived from mouse models at different stages of viral myocarditis (GSE35182). Functional annotation was executed within the key modules. Potential hub genes were predicted based on the intramodular connectivity (IC). Finally, potential microRNAs that regulate gene expression were predicted by miRNet analysis.

Results: Three gene co-expression modules showed the strongest correlation with the acute or chronic disease stage. A significant positive correlation was detected between the acute disease stage and the turquoise module, the genes of which were mainly enriched in antiviral response and immune-inflammatory activation. Furthermore, a significant positive correlation and a negative correlation were identified between the chronic disease stage and the brown and yellow modules, respectively. These modules were mainly associated with the cytoskeleton, phosphorylation, cellular catabolic process, and autophagy. Subsequently, we predicted the underlying hub genes and microRNAs in the three modules.

Conclusions: This study revealed the main biological processes in different stages of viral myocarditis and predicted hub genes in both the acute and chronic disease stages. Our results may be helpful for developing new therapeutic targets for viral myocarditis in future research.
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http://dx.doi.org/10.21037/atm-20-3337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723587PMC
November 2020

A machine learning-based approach for the prediction of periprocedural myocardial infarction by using routine data.

Cardiovasc Diagn Ther 2020 Oct;10(5):1313-1324

Department of Cardiology, Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) is associated with the bad prognosis in patients. Current approaches to predict PMI fail to identify many people who would benefit from preventive treatment, and machine learning (ML) offers opportunity to improve the performance of ML models for PMI based on the big routine data.

Methods: By using electronic medical records, we retrospectively extracted all records of patients from 2007 to 2019 in our cardiovascular center. The main enrollment criterion was that inpatients with one single coronary stenosis with stents implantation this time. The primary outcome was PMI [PMI3: cTnI >3-fold upper reference limit (URL); PMI5: cTnI >5-fold URL]. Four different ML algorithms [Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), Artificial Neural Networks (ANN)] were evaluated and their diagnostic accuracy measures were compared.

Results: A total of (10,886) patients who were admitted in our hospital. PMI3 and PMI5 results were analyzed respectively. The incidence of PMI3 and PMI5 was 20.9% and 13.7%. In PMI3 Drop group, ANN (accuracy: 0.72; AUC: 0.77) showed the best power to predict the presence of PMI; In PMI3 Mean Group, RF (accuracy: 0.72; AUC: 0.77) showed the best power; In PMI5 Drop group, RF (accuracy: 0.67; AUC: 0.67) showed the best power; In PMI5 Mean group, RF (accuracy: 0.61; AUC: 0.67) showed the best power.

Conclusions: ML methods may provide accurate prediction of PMI in CAD patients, and could be used as a precise model in the preventive treatment of PMI.
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http://dx.doi.org/10.21037/cdt-20-551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666922PMC
October 2020

Impact of increased inflammation biomarkers on periprocedural myocardial infarction in patients undergoing elective percutaneous coronary intervention: a cohort study.

J Thorac Dis 2020 Oct;12(10):5398-5410

Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: The fact that each inflammatory indicator has a forecasting capacity on the occurrence of periprocedural myocardial infarction (PMI) has a controversial existence. The purpose of this study was to explore the role of inflammation biological indicators on PMI in a group of patients undergoing selective percutaneous coronary intervention (PCI).

Methods: The study was carried out both in a retrospective and prospective manner in 7,413 and 1,189 subjects, respectively. In the retrospective cohort study, the association between inflammation biomarkers and PMI was assessed by univariate and multivariate logistic regression. WBC, CRP, and NLR were distributed using k-means clustering into a virtual variable "Inflammatory Trend", and multivariate logistic regression and subgroup analysis were performed. In the prospective cohort study, the endpoints were PMI, cardiovascular death or cardiac arrest. The chi-square test was performed to calculate the relative risk (RR).

Results: In the retrospective cohort study, except WBC, CRP, NLR and virtual variable "Inflammatory trend" were independent risk factors for PMI. The subgroup analysis revealed that CRP can serve as the most stable predictor. In the prospective cohort study, WBC (RR =1.134, P=0.416) has no effect on the incidence of PMI. However, an elevation in the incidence of PMI was observed with an increase of NLR (RR =1.354, P=0.041) and CRP (RR =1.412, P=0.025).

Conclusions: In patients with elective PCI for single-vessel lesions, high CRP increases the risk for PMI. The increase of NLR was an independent risk factor for PMI, especially for patients with hypertension and under the age of 70. WBC has no influence on the occurrence of PMI.
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http://dx.doi.org/10.21037/jtd-20-1605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656373PMC
October 2020

Rapid reversal of heart failure by correcting left bundle branch block induced by transcatheter aortic valve replacement.

Pacing Clin Electrophysiol 2021 01 1;44(1):203-207. Epub 2020 Dec 1.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University of Medicine, Hangzhou, PR China.

Transcatheter aortic valve replacement (TAVR) induced pathological damage in cardiac conduction system leads to symptomatic bradycardia and electric dyssynchrony such as left bundle branch block (LBBB) is associated with an increased risk for heart failure. Left bundle branch pacing (LBBP) has emerged as an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle. We report a case of heart failure patient with new onset LBBB (NO-LBBB) induced by TAVR, LBBP corrected the NO-LBBB and reversed the heart function with stable capture and correction threshold.
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http://dx.doi.org/10.1111/pace.14132DOI Listing
January 2021

Impact of Minimally Invasive Esophagectomy in Post-Operative Atrial Fibrillation and Long-Term Mortality in Patients Among Esophageal Cancer.

Cancer Control 2020 Jan-Dec;27(1):1073274820974013

Department of Cardiology of Sir Run Run Shaw Hospital, 56660Zhejiang University School of Medicine, Hangzhou, Zhejiang province, China.

Aims: Postoperative Atrial fibrillation (POAF) after esophagectomy may prolong stay in intensive care and increase risk of perioperative complications. A minimally invasive approach is becoming the preferred option for esophagectomy, yet its implications for POAF risk remains unclear. The association between POAF and minimally invasive esophagectomy (MIE) was examined in this study.

Methods: We used a dataset of 575 patients who underwent esophagectomy. Multivariate logistic regression analysis was performed to examine the association between MIE and POAF. A cox proportional hazards model was applied to assess the long-term mortality (MIE vs open esophagectomy, OE).

Results: Of the 575 patients with esophageal cancer, 62 developed POAF. MIE was negatively associated with the occurrence of POAF (Odds ratio: 0.163, 95%CI: 0.033-0.801). No significant difference was observed in long-term mortality (Odds ratio: 2.144, 95%CI: 0.963-4.775).

Conclusions: MIE may reduced the incidence of POAF without compromising the survival of patients with esophageal cancer. Moreover, the specific mechanism of MIE providing this possible advantage needs to be determined by larger prospective cohort studies with specific biomarker information from laboratory tests.
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http://dx.doi.org/10.1177/1073274820974013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791452PMC
November 2020

The impact of homocysteine on the risk of coronary artery diseases in individuals with diabetes: a Mendelian randomization study.

Acta Diabetol 2021 Mar 28;58(3):301-307. Epub 2020 Oct 28.

Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, People's Republic of China.

Aims: Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes.

Methods: A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test.

Results: The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82-1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: - 0.08-0.03, p = 0.35).

Conclusion: This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.
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http://dx.doi.org/10.1007/s00592-020-01608-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907016PMC
March 2021

Effect of Shexiang Tongxin dropping pill on stable coronary artery disease patients with normal fractional flow reserve and coronary microvascular disease: A study protocol.

Medicine (Baltimore) 2020 Sep;99(38):e22126

Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Introduction: Coronary microvascular disease (CMVD) can affect the structure, function, and metabolism of the heart, and has an important impact on the occurrence, development and prognosis of coronary artery disease (CAD). Shexiang Tongxin dropping pill (STDP) can dilate blood vessels, alleviate inflammation, reduce endothelial damage, and improve coronary microvascular function in mice with myocardial infarction. This study aims to assess the impact of STDP on stable coronary artery disease (SCAD) patients with normal FFR and CMVD.

Methods And Analysis: This is a single-center, prospective randomized trial that will enroll 64 SCAD patients, CAD with normal FFR and CMVD. Patients will be randomly divided into study group and control group in a 1:1 fashion. On the basis of conventional drug treatment, the former will receive STDP while the latter will not. The follow-up period of the subjects is 12 months, and clinical follow-up will be conducted before discharge, 30 days, 3 months, 6 months, and 12 months after procedure to complete the detection of relevant indicators. The primary endpoint is the change of index of microcirculatory resistance (ΔIMR) at 12-month follow-up.

Discussion: The present study will be the first randomized control study to evaluate the efficacy and safety of STDP on SCAD patients, CAD with normal FFR and CMVD, which will provide a broader idea and more experimental basis for improving the treatment of CMVD.

Trial Registration: This is a protocol for the randomized clinical trial which has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR2000032429.
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http://dx.doi.org/10.1097/MD.0000000000022126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505333PMC
September 2020

The role of surgery type in postoperative atrial fibrillation and in-hospital mortality in esophageal cancer patients with preserved left ventricular ejection fraction.

World J Surg Oncol 2020 Sep 11;18(1):244. Epub 2020 Sep 11.

Department of Cardiology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Zhejiang, 310000, Hangzhou, China.

Background: Postoperative atrial fibrillation (POAF) is one of the most common complications of esophagectomy, which may extend the inpatient hospital stay. Minimally invasive esophagectomy (MIE) has been increasingly used in clinical practice; however, its POAF risk and short-term mortality remain unclear. This study aimed to examine the POAF risk and in-hospital mortality rate between patients receiving MIE and open esophagectomy (OE).

Methods: Esophageal cancer patients who underwent MIE or OE from a retrospective cohort study were evaluated. A multivariate logistic regression model was built to assess the associations between esophagectomy (MIE vs. OE) and various outcomes (POAF, in-hospital mortality). Covariates included age, sex, body mass index, neoadjuvant therapy, tumor stage, surgery incision type, comorbidities, cardia conditions, peri-operative medication, and complications.

Results: Of the 484 patients with esophageal cancer, 63 received MIE. A total of 53 patients developed POAF. Compared to patients receiving OE, MIE patients had 81% reduced odds of POAF (adjusted odds ratio [aOR] 0.185, 95% CI 0.039-0.887, P = 0.035). No statistically significant association was found for in-hospital mortality (aOR 0.709, 95% CI 0.114-4.409, P = 0.712).

Conclusions: MIE is associated with a lower risk of POAF, compared to traditional surgery. No significant short-term survival benefit was found for MIE.
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http://dx.doi.org/10.1186/s12957-020-02011-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488674PMC
September 2020

The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway.

J Cell Physiol 2021 Mar 11;236(3):2058-2069. Epub 2020 Aug 11.

The Key Laboratory of Myocardial Ischaemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang, China.

The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein-1 and interleukin-10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-βR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.
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http://dx.doi.org/10.1002/jcp.29993DOI Listing
March 2021

Detection of peripherally inserted central catheter (PICC) in chest X-ray images: A multi-task deep learning model.

Comput Methods Programs Biomed 2020 Dec 23;197:105674. Epub 2020 Jul 23.

Department of Nursing, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China, 310009. Electronic address:

Background And Objective: Peripherally inserted central catheter (PICC) is a novel drug delivery mode which has been widely used in clinical practice. However, long-term retention and some improper actions of patients may cause some severe complications of PICC, such as the drift and prolapse of its catheter. Clinically, the postoperative care of PICC is mainly completed by nurses. However, they cannot recognize the correct position of PICC from X-ray chest images as soon as the complications happen, which may lead to improper treatment. Therefore, it is necessary to identify the position of the PICC catheter as soon as these complications occur. Here we proposed a novel multi-task deep learning framework to detect PICC automatically through X-ray images, which could help nurses to solve this problem.

Methods: We collected 348 X-ray chest images from 326 patients with visible PICC. Then we proposed a multi-task deep learning framework for line segmentation and tip detection of PICC catheters simultaneously. The proposed deep learning model is composed of an extraction structure and three routes, an up-sampling route for segmentation, an RPNs route, and an RoI Pooling route for detection. We further compared the effectiveness of our model with the models previously proposed.

Results: In the catheter segmentation task, 300 X-ray images were utilized for training the model, then 48 images were tested. In the tip detection task, 154 X-ray images were used for retraining and 20 images were used in the test. Our model achieved generally better results among several popular deep learning models previously proposed.

Conclusions: We proposed a multi-task deep learning model that could segment the catheter and detect the tip of PICC simultaneously from X-ray chest images. This model could help nurses to recognize the correct position of PICC, and therefore, to handle the potential complications properly.
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http://dx.doi.org/10.1016/j.cmpb.2020.105674DOI Listing
December 2020

Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing.

JACC Clin Electrophysiol 2020 07;6(7):849-858

University of Chicago Medicine, Center for Arrhythmia Care, Pritzker School of Medicine, Department of Medicine, Section of Cardiology, Chicago, Illinois, USA.

Objectives: The aim of this study was to assess the feasibility and efficacy of left bundle branch pacing (LBBP) using a novel intraseptal technique to deliver cardiac resynchronization therapy (CRT) in patients with left bundle branch block (LBBB) and nonischemic cardiomyopathy.

Background: His bundle pacing to correct LBBB is a viable alternative approach to achieve CRT but is limited by suboptimal lead delivery and high thresholds.

Methods: This was a prospective, multicenter study performed between June 2017 and August 2018 at 6 centers. Patients with nonischemic cardiomyopathy, complete LBBB, and left ventricular ejection fractions (LVEFs) ≤50% who had indications for CRT and/or ventricular pacing in whom LBBP was attempted were included. Success rates, QRS duration, LVEF, left ventricular end-systolic volume, and improvement in functional class were assessed.

Results: LBBP was successful in 61 of 63 patients (97%, mean age 68 ± 11 years, 52.4% men). During LBBP, QRS duration narrowed from 169 ± 16 to 118 ± 12 ms (p < 0.001). Pacing threshold and R-wave amplitude remained stable at 1-year follow-up compared with implantation values (0.5 ± 0.15 V/0.5 ms vs. 0.58 ± 0.14 V/0.5 ms and 11.1 ± 4.9 mV vs. 13.3 ± 5.3 mV, respectively). LVEF increased significantly (33 ± 8% vs. 55 ± 10%; p < 0.001), with a reduction in left ventricular end-systolic volume (123 ± 61 ml vs. 67 ± 39 ml; p < 0.001). LVEF had normalized (≥50%) in 75% of patients at 1 year. New York Heart Association functional class improved significantly from 2.8 ± 0.6 at baseline to 1.4 ± 0.6 at 1 year. No deaths or heart failure hospitalizations were observed during follow-up.

Conclusions: LBBP is a feasible and effective method for achieving electric resynchronization of LBBB, with resultant improvements in left ventricular structure and function. Low and stable pacing thresholds may be advantageous over His bundle pacing for CRT in patients with LBBB and nonischemic cardiomyopathy.
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http://dx.doi.org/10.1016/j.jacep.2020.04.011DOI Listing
July 2020

[Prognosis of patients with vulnerable plaques indicated by coronary CT angiography].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 May;49(1):76-81

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.

Objective: To investigate the prognosis of patients with vulnerable plaque indicated by coronary CT angiography (CCTA).

Methods: Totally 1963 patients underwent CCTA from February 2nd 2015 to September 13th 2015, and 2728 coronary borderline lesions (stenosis of 50%-70%) were detected. Among them 804 patients had vulnerable plaques and 1159 patients had stable plaques. The primary endpoint was major cardiac adverse events (MACE), including cardiac death, acute myocardial infarction and target lesion revascularization.

Results: Patients were followed up for a mean follow-up of 27.4±2.3 months. The incidence of MACE in the vulnerable plaque group was significantly higher than that in the stable plaque group (10.8%vs 2.3%, < 0.01). After adjusting for age, gender, smoking, hypertension, diabetes, hyperlipidemia, the MACE hazard ratio () in the vulnerable plaque group was 5.022 (95% :3.254-7.751, < 0.01).Subgroup analysis showed that in the vulnerable plaque group, the incidence of MACE in patients taking antiplatelet and statin ≤3 months and those taking antiplatelet and statin > 3 months was 17.0%and 5.8%, respectively (=3.149, 95% :1.987-4.992, < 0.01); but the difference did not seen in stable plaque group (=1.721, 95% :0.798-3.712, >0.05).

Conclusions: This study confirmed the risk of MACE in patients with vulnerable plaque detected by CCTA and the drug treatment may reduce the risk for patients with vulnerable plaque.
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May 2020

Intracardiac ultrasound-guided left bundle branch pacing in a bradycardia patient.

Clin Case Rep 2020 Jun 11;8(6):1030-1033. Epub 2020 Mar 11.

Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University of Medicine Hangzhou China.

Left bundle branch pacing was associated with narrower QRS in patients with pacemaker indications. LBBP guided by ICE improves the accuracy of LBBP, facilitates the lead localization, minimizes complications, and above all reduces radiation exposure time.
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http://dx.doi.org/10.1002/ccr3.2798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303858PMC
June 2020

Effect of preoperative gabapentin after transurethral prostate resection under general anesthesia. A randomized double-blind, placebo-controlled trial.

Saudi Med J 2020 Jun;41(6):640-644

Department of Urology, The First Hospital of Jilin University, Jilin, China. E-mail.

Objectives: To investigate whether preoperative oral gabapentin could reduce postoperative pain, analgesic consumption and the occurrence of catheter-related bladder discomfort (CRBD). Methods: In this study, participants randomly received either 600 mg gabapentin or placebo orally 2 h prior to transurethral prostate resection. Visual analogue scale and Ramsay sedation scale was utilized to assess pain intensity and sedation status after surgery. Intravenous 1.5 mg.kg-1 tramadol was used for postoperative analgesia. Pain intensity, sedation status, CRBD, tramadol consumption, side effects and the overall satisfaction degree were assessed and recorded for 48 h after tracheal extubation.  Results: Ninety participants given gabapentin and 91 participants given placebo completed the study. Lower visual analogue scale scores, less tramadol consumption, longer time to the first analgesic requirement, lower incidence of CRBD and nausea and higher satisfaction degree were detected in the patients receiving gabapentin compared with the patients receiving placebo.  Conclusion: Preoperative oral gabapentin reduced postoperative visual analogue scale scores, tramadol consumption and the occurrence rate of CRBD and nausea, and consequently, increased the degree of patients' satisfaction after transurethral prostate resection.
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http://dx.doi.org/10.15537/smj.2020.6.25132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502946PMC
June 2020

TANK-binding kinase 1 alleviates myocardial ischemia/reperfusion injury through regulating apoptotic pathway.

Biochem Biophys Res Commun 2020 07 3;528(3):574-579. Epub 2020 Jun 3.

Department of Cardiology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, 310020, Hangzhou, Zhejiang, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang, China. Electronic address:

Myocardial ischemia/reperfusion (MI/R) injury, a complicated pathophysiological process, is regulated by lots of signaling pathways. Here in our present study, we identified TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, as a protective regulator in MI/R injury. Our results indicated that TBK1 was decreased in MI/R injury in mice. However, after overexpressing TBK1 through an intramyocardial injection of TBK1 adenovirus, TBK1 overexpression improved cardiac function detected by echocardiography, decreased infarct size detected by Evans Blue and TTC staining, reduced cardiomyocyte apoptosis measured by TUNEL staining and alleviated disruption of mitochondria and cardiac muscle fibers detected by TEM in response to MI/R injury. Consistently, TBK1 overexpression ameliorated mitochondrial oxygen consumption rate (OCR) in neonatal rat cardiomyocytes (NRCMs) in response to hypoxia/reoxygenation (H/R) injury. Mechanistically, TBK1 overexpression upregulated Bcl-2 (an anti-apoptotic protein) but downregulated Bax (a pro-apoptotic protein) in vivo and in vitro. Collectively, our findings uncovered a pivotal function of TBK1 in MI/R injury through regulating the levels of apoptotic proteins for the first time, which might represent a promising target in treating MI/R patients in the future.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.143DOI Listing
July 2020

Variability in blood lipids affects the neutrophil to lymphocyte ratio in patients undergoing elective percutaneous coronary intervention: a retrospective study.

Lipids Health Dis 2020 Jun 3;19(1):124. Epub 2020 Jun 3.

Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No 3 East of Qinchun Road, Hangzhou, Zhejiang, 310000, People's Republic of China.

Background: Atherosclerosis is associated with chronic inflammation and lipid metabolism. The neutrophil to lymphocyte ratio (NLR) as an indicator of inflammation has been confirmed to be associated with cardiovascular disease prognosis. However, few studies have explored the effects of blood lipid variability on NLR. The aim of this study was to explore the relationship between variability in blood lipid levels and NLR.

Methods: The association between variability in blood lipids and NLR was assessed with both univariate and multivariate linear regression. Multivariate linear regression was also performed for a subgroup analysis.

Results: The variability of high-density lipoprotein cholesterol (HDL-C) (regression coefficients [β] 4.008, standard error (SE) 0.503, P-value< 0.001) and low-density lipoprotein cholesterol (LDL-C) ([β] 0.626, SE 0.164, P-value< 0.001) were risk factors for the NLR value, although baseline LDL-C and HDL-C were not risk factors for NLR values. Variability of HDL-C ([β] 4.328, SE 0.578, P-value< 0.001) and LDL-C ([β] 0.660, SE 0.183, P-value< 0.001) were risk factors for NLR variability. Subgroup analysis demonstrated that the relationship between variability of LDL-C and NLR was consistent with the trend of the total sample for those with diabetes mellitus, controlled blood lipid, statins, atorvastatin. The relationship between the variability of HDL-C and NLR was consistent with the trend of the total sample in all subgroups.

Conclusion: The variability of HDL-C and LDL-C are risk factors for the value and variability of NLR, while the relationship between variability of HDL-C and NLR is more stable than the variability of LDL-C in the subgroup analysis, which provides a new perspective for controlling inflammation in patients undergoing PCI.
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http://dx.doi.org/10.1186/s12944-020-01304-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271440PMC
June 2020

Esophageal contraction during cryoablation: A possible protective mechanism.

Pacing Clin Electrophysiol 2020 09 21;43(9):908-912. Epub 2020 Aug 21.

Heart Institute, Cedars Sinai Medical Center, Los Angeles, California.

Background: Contraction of the esophagus was observed during cryoablation for paroxysmal atrial fibrillation (PAF). The purpose of this study is to investigate the mechanism of esophageal contraction and the correlation between the contraction and esophageal thermal lesions.

Methods: This prospective study enrolled 64 patients with PAF undergoing second-generation cryoballoon (CB2) ablation for pulmonary vein isolation (PVI). During PVI for the left inferior pulmonary vein, contrast esophagography was performed before and during cryoablation. The sample population was divided into two groups: A (31 patients) and B (33 patients). Group A consisted of patients in whom the distal half of the CB was in proximity to the esophagus, while for group B the esophagus was away from the distal half of the CB. Esophageal contraction was recorded as a variation in the width of the esophageal lumen during PVI. Postablation esophageal endoscopy was done on all patients.

Results: The reduction in the width of the esophageal lumen in group A was greater than in group B during freezing (40.12 ± 23.24% vs 8.14 ± 10.35%, P < .001). Following endoscopy, no apparent esophageal lesion was detected in all patients.

Conclusion: The extent of esophageal contraction is correlated with the positioning of the esophagus at the distal half of the CB. The findings of this study indicate that esophageal contraction during freezing may be a self-protective mechanism.
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http://dx.doi.org/10.1111/pace.13967DOI Listing
September 2020

Primary prevention of myocardial infarction: aspirin is not as useful as it seems.

Ann Transl Med 2020 Mar;8(6):361

Department of Cardiology, Provincial Key Laboratory of Cardiovascular Intervention and Heart Regeneration, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.

Background: Aspirin has not been reliably shown to reduce all-cause and cardiovascular mortality but can prevent symptomatic myocardial infarction. However, silent myocardial infarction (SMI) is not uncommon in clinical practice. No meta-analysis has compared the effect of aspirin administration on primary prevention of all myocardial infarctions, including SMI.

Methods: We systematically searched PubMed, Embase, Web of Science, Cochrane Library and Google Scholar for randomized double-blind controlled trials evaluating the effect of aspirin on primary prevention of all myocardial infarctions, including SMI.

Results: The current meta-analysis included 9 trials involving 67,486 patients and 67,557 controls on aspirin primary prevention of all myocardial infarctions. When SMI was included in the total number of myocardial infarctions, the aspirin effect on the primary prevention of myocardial infarction was not as significant as expected [risk ratio (RR): 0.883; 95% confidence interval (CI): 0.780 to 1.001; P=0.052].

Conclusions: Aspirin may not provide a primary preventive effect in all myocardial infarction patients. Previously demonstrated reductions in myocardial infarction are not present when SMI is included.
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http://dx.doi.org/10.21037/atm.2020.02.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186645PMC
March 2020

Inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy.

Ann Transl Med 2020 Mar;8(6):293

Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.

Background: Contrast induced diabetic nephropathy (CIN) is an important cause of hospital-acquired acute renal failure. Our aim was to observe the effect of protein kinase C β2 (PKCβ2) knockdown on human proximal tubular epithelial cells (HK-2 cells) against meglumine diatrizoate and advanced glycation end products (AGEs)-induced apoptosis and autophagy.

Methods: Cell viability was detected using cell counting kit-8 (CCK-8) assay in HK-2 cells after disposal with meglumine diatrizoate and AGEs with or without PKCβ2 siRNA/inhibitor LY333531. Flow cytometry and western blot were used to test cell apoptosis and the related protein levels in meglumine diatrizoate and AGEs co-treated HK-2 cells with or without PKCβ2 siRNA/inhibitor LY333531. Autophagy related proteins were detected using western blot. Immunofluorescence staining was used to examine the autophagy-specific protein light chain 3 (LC3), and autophagosome and autolysosome formation was observed under a transmission electron microscopy.

Results: CCK-8 assay results showed that meglumine diatrizoate inhibited AGEs-induced HK-2 cell viability. Furthermore, meglumine diatrizoate promoted cell apoptosis and the expression level of caspase3 in AGEs-induced HK-2. Western blot results showed that meglumine diatrizoate elevated the expression levels of PKCβ2 and p-PKCβ2 in AGEs-induced HK-2 cells, and up-regulated the expression level of Beclin-1 and the ratio of LC3 II/LC3 I, and down-regulated the expression level of p62 in AGEs-induced HK-2 cells. We found that PKCβ2 knockdown alleviated meglumine diatrizoate and AGEs-induced HK-2 cell apoptosis and autophagy. Intriguingly, PKCβ2 inhibitor LY333531 reversed 3-methyladenine (3-MA)-induced autophagy inhibition in meglumine diatrizoate and AGEs-induced HK-2 cells.

Conclusions: Our findings reveal that inhibiting PKCβ2 protects HK-2 cells against meglumine diatrizoate and AGEs-induced apoptosis and autophagy, which provide a novel therapeutic insight for CIN in diabetic patients.
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http://dx.doi.org/10.21037/atm.2020.02.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186606PMC
March 2020

Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).

Int J Mol Med 2020 May 20;45(5):1275-1293. Epub 2020 Feb 20.

Department of Vascular Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Thrombospondin (TSP)‑1 and TSP‑2 are matricellular proteins in the extracellular matrix (ECM), which serve a significant role in the pathological processes of various cardiovascular diseases (CVDs). The multiple effects of TSP‑1 and TSP‑2 are due to their ability to interact with various ligands, such as structural components of the ECM, cytokines, cellular receptors, growth factors, proteases and other stromal cell proteins. TSP‑1 and TSP‑2 regulate the structure and activity of the aforementioned ligands by interacting directly or indirectly with them, thereby regulating the activity of different types of cells in response to environmental stimuli. The pathological processes of numerous CVDs are associated with the degradation and remodeling of ECM components, and with cell migration, dysfunction and apoptosis, which may be regulated by TSP‑1 and TSP‑2 through different mechanisms. Therefore, investigating the role of TSP‑1 and TSP‑2 in different CVDs and the potential signaling pathways they are associated with may provide a new perspective on potential therapies for the treatment of CVDs. In the present review, the current understanding of the roles TSP‑1 and TSP‑2 serve in various CVDs were summarized. In addition, the interacting ligands and the potential pathways associated with these thrombospondins in CVDs are also discussed.
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http://dx.doi.org/10.3892/ijmm.2020.4507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138268PMC
May 2020