Publications by authors named "Xinping Luo"

87 Publications

Long-term association of ambient air pollution and hypertension in adults and in children: A systematic review and meta-analysis.

Sci Total Environ 2021 Nov 7;796:148620. Epub 2021 Jul 7.

Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong, China. Electronic address:

Aims: The association of long-term ambient air pollution and hypertension has been inconsistently reported. We performed an updated systematic review and meta-analysis to assess the association between long-term exposure to ambient air pollution and risk of hypertension in adults and in children.

Methods: PubMed, EMBASE, and Web of Science were searched up to August 7, 2020 for published articles examining the association of long-term exposure to ambient air pollution, including particulate matter (PM; ultrafine particles, PM, PM, PM, PM and PM), nitrogen dioxide (NO), nitrogen oxides (NO), sulfur dioxide (SO), ozone (O), carbon monoxide (CO) and hypertension. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension with each 10-μg/m increase in air pollutants were calculated by random-effects models.

Results: We included 57 studies (53 of adults and 4 of children) in the meta-analysis. Risk of hypertension was significantly increased in adults with each 10-μg/m increase in exposure to PM (OR 1.10, 95% CI 1.07-1.14; I = 93.1%; n = 37), PM (1.04, 1.02-1.07; I = 44.8%; n = 22), and SO (1.21, 1.08-1.36; I = 96.6%; n = 3). Hypertension was not significantly associated with PM (n = 2), PM (n = 16), NO (n = 27), or NO (n = 17). In children, the summary ORs (95% CIs) for each 10-μg/m increase in PM, PM, SO and O were 2.82 (0.51-15.68; I = 83.8%; n = 2), 1.15 (1.01-1.32; I = 0; n = 2), 8.57 (0.13-575.58; I = 94.2%; n = 2), and 1.26 (0.81-1.09, I = 91.6%; n = 2), respectively.

Conclusions: Long-term ambient air pollution is a potential risk factor for hypertension in adults. More studies are needed to explore the effects of long-term air pollution on hypertension in children.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148620DOI Listing
November 2021

Prediction of all-cause mortality with malnutrition assessed by controlling nutritional status score in patients with heart failure: a systematic review and meta-analysis.

Public Health Nutr 2021 Jun 30:1-8. Epub 2021 Jun 30.

Department of Cardiology, Huashan Hospital, Fudan University, No.12, Mid Urumuqi Road, Jingan District, Shanghai200040, People's Republic of China.

Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure.

Design: Systematic review and meta-analysis.

Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase.

Participants: Ten studies involving 5196 patients with heart failure.

Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up.

Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.
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http://dx.doi.org/10.1017/S1368980021002470DOI Listing
June 2021

Ablation of incisional re-entrant atrial tachycardia via superior approach in heterotaxy syndrome.

Europace 2021 08;23(8):1261

Department of Cardiology, Huashan Hospital Fudan University, 12 Wulumuqizhong Road, Shanghai 200040, China.

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http://dx.doi.org/10.1093/europace/euab094DOI Listing
August 2021

Metabolizable Near-Infrared-II Nanoprobes for Dynamic Imaging of Deep-Seated Tumor-Associated Macrophages in Pancreatic Cancer.

ACS Nano 2021 06 1;15(6):10010-10024. Epub 2021 Jun 1.

Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China.

Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer. Herein, we aim to develop metabolizable dextran-indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose radiotherapy and zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision therapy in pancreatic cancer.
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http://dx.doi.org/10.1021/acsnano.1c01608DOI Listing
June 2021

Fried-food consumption and risk of cardiovascular disease and all-cause mortality: a meta-analysis of observational studies.

Heart 2021 Oct 19;107(19):1567-1575. Epub 2021 Jan 19.

Department of Biostatistics and Epidemiology, Shenzhen University Health Science Center, Shenzhen, Guangdong, China

Objective: We performed a meta-analysis, including dose-response analysis, to quantitatively determine the association of fried-food consumption and risk of cardiovascular disease and all-cause mortality in the general adult population.

Methods: We searched PubMed, EMBASE and Web of Science for all articles before 11 April 2020. Random-effects models were used to estimate the summary relative risks (RRs) and 95% CIs.

Results: In comparing the highest with lowest fried-food intake, summary RRs (95% CIs) were 1.28 (1.15 to 1.43; n=17, I=82.0%) for major cardiovascular events (prospective: 1.24 (1.12 to 1.38), n=13, I=75.7%; case-control: 1.91 (1.15 to 3.17), n=4, I=92.1%); 1.22 (1.07 to 1.40; n=11, I=77.9%) for coronary heart disease (prospective: 1.16 (1.05 to 1.29), n=8, I=44.6%; case-control: 1.91 (1.05 to 3.47), n=3, I=93.9%); 1.37 (0.97 to 1.94; n=4, I=80.7%) for stroke (cohort: 1.21 (0.87 to 1.69), n=3, I=77.3%; case-control: 2.01 (1.27 to 3.19), n=1); 1.37 (1.07 to 1.75; n=4, I=80.0%) for heart failure; 1.02 (0.93 to 1.14; n=3, I=27.3%) for cardiovascular mortality; and 1.03 (95% CI 0.96 to 1.12; n=6, I=38.0%) for all-cause mortality. The association was linear for major cardiovascular events, coronary heart disease and heart failure.

Conclusions: Fried-food consumption may increase the risk of cardiovascular disease and presents a linear dose-response relation. However, the high heterogeneity and potential recall and misclassification biases for fried-food consumption from the original studies should be considered.
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http://dx.doi.org/10.1136/heartjnl-2020-317883DOI Listing
October 2021

Pseudo normalization of H-V interval due to intra-His block in a patient with fasciculoventricular accessory pathway.

J Electrocardiol 2021 Jan-Feb;64:9-11. Epub 2020 Nov 20.

Department of Cardiology, Huashan Hospital Fudan University, 12 Wulumuqizhong Road, Shanghai 200040, China. Electronic address:

A 57-year-old male suffering from cardiogenic syncope was found to have preexcited QRS on surface ECG at admission. A dual-chamber ICD was implanted after discovering intermittent high degree A-V block and ventricular tachycardia during hospitalization. An EP study was performed 2 days later. Fasciculoventricular accessory pathway was diagnosed based on the fixed H-V interval with different A-H interval when atrial activation conducted to ventricle. However, the H-V interval was normal, which can be explained by intra-His block based on the findings of two split His potentials, the second of which was closely followed by local ventricular electrogram. The conduction delay in His bundle led to pseudo normalization of H-V interval.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.11.010DOI Listing
June 2021

Increased serum interleukin-6 level as a predictive biomarker for atrial fibrillation: A systematic review and meta-analysis.

Rev Port Cardiol (Engl Ed) 2020 Dec 21;39(12):723-728. Epub 2020 Nov 21.

Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China. Electronic address:

Background: Atrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy.

Methods: We conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF.

Results: A total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p<0.001) and all-cause mortality (RR 2.35, CI 95% 2.09-2.65, p<0.001).

Conclusion: A higher level of IL-6 may predict a greater number of long-term thromboembolic events and bleeding events, ACS events and mortality in AF patients. Further studies such as the cut-off point of IL-6 need to be conducted in the future.
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http://dx.doi.org/10.1016/j.repc.2020.07.009DOI Listing
December 2020

Association of TG/HDLC ratio trajectory and risk of type 2 diabetes: A retrospective cohort study in China.

J Diabetes 2020 Oct 19. Epub 2020 Oct 19.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center, Shenzhen, People's Republic of China.

Background: The association of ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio) change trajectory with risk of type 2 diabetes mellitus (T2DM) remains unknown. The aim of this study was to evaluate the association between risk of T2DM and TG/HDL-C ratio change trajectory.

Methods: A total of 18 444 participants aged 18-80 years old were included in this cohort study. Linear regression and quadratic regression models were used to determine the TG/HDL-C ratio change trajectory. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TG/HDL-C ratio change trajectory and probability of T2DM.

Results: T2DM developed in 714 participants during a median follow-up of 5.74 years (92 076.23 person-years of follow-up). After adjusting for baseline potential confounders, odds of T2DM were greater for participants with the increasing, U-shape, bell-shape, and other shape change vs decreasing change (adjusted OR [aOR] 2.01, 95% CI 1.42-2.81; 1.56, 1.15-2.13; 1.60, 1.17-2.20; and 1.49, 1.13-2.00, respectively). The results were robust in the sensitivity analyses on excluding baseline participants with T2DM. Moreover, the associations remained significant with male sex, age <60 years and body mass index <24 kg/m .

Conclusions: This retrospective study revealed increased probability of T2DM with increasing, U-shape, bell-shape, and other-shape TG/HDL-C ratio change trajectories, especially with male sex, age <60 years and body mass index <24 kg/m .
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http://dx.doi.org/10.1111/1753-0407.13123DOI Listing
October 2020

PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36.

Circulation 2021 Jan 29;143(1):45-61. Epub 2020 Sep 29.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (Z.Q., W.Y., D.J., Z.Y., K.Y., A.S., J.Q., J.G.).

Background: PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear.

Methods: We detected the direct effects of PCSK9 on agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, α-granule release, spreading, and clot retraction. These studies were complemented by in vivo analysis of FeCl-injured mouse mesenteric arteriole thrombosis. We also investigated the underlying mechanisms. Using the myocardial infarction (MI) model, we explored the effects of PCSK9 on microvascular obstruction and infarct expansion post-MI.

Results: PCSK9 directly enhances agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, P-selectin release from α-granules, spreading, and clot retraction. In line, PCSK9 enhances in vivo thrombosis in a FeCl-injured mesenteric arteriole thrombosis mouse model, whereas PCSK9 inhibitor evolocumab ameliorates its enhancing effects. Mechanism studies revealed that PCSK9 binds to platelet CD36 and thus activates Src kinase and MAPK (mitogen-activated protein kinase)-extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase, increases the generation of reactive oxygen species, and activates the p38MAPK/cytosolic phospholipase A2/cyclooxygenase-1/thromboxane A signaling pathways downstream of CD36 to enhance platelet activation, as well. Using CD36 knockout mice, we showed that the enhancing effects of PCSK9 on platelet activation are CD36 dependent. It is important to note that aspirin consistently abolishes the enhancing effects of PCSK9 on platelet activation and in vivo thrombosis. Last, we showed that PCSK9 activating platelet CD36 aggravates microvascular obstruction and promotes MI expansion post-MI.

Conclusions: PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis, and MI expansion post-MI, as well, by binding to platelet CD36 and thus activating the downstream signaling pathways. PCSK9 inhibitors or aspirin abolish the enhancing effects of PCSK9, supporting the use of aspirin in patients with high plasma PCSK9 levels in addition to PCSK9 inhibitors to prevent thrombotic complications.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046290DOI Listing
January 2021

Efficient and targeted chemo-gene delivery with self-assembled fluoro-nanoparticles for liver fibrosis therapy and recurrence.

Biomaterials 2020 12 8;261:120311. Epub 2020 Aug 8.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

The treatment options of liver fibrosis remain limited except for liver transplantation due to the complexity and slow development in its progression. Besides, liver fibrosis recurrence and intervention time have not been reported as significant indicators to affect the anti-fibrotic efficacy of tested drugs/strategies. Herein, a novel fluoropolymer is developed to achieve high drug loading of sorafenib and efficient delivery of miR155 inhibitor (anti-miR155) for dual-targeting of hepatic stellate cells (HSCs) and kupffer cells (KCs), and we report a detailed plan on the design of treatment regimen to reveal the relationship between chemogene therapy, intervention time and fibrosis recurrence. Such a combined chemo-gene therapy of sorafenib and anti-miR155 can achieve superior therapeutic efficiency by polarizing the pro-inflammatory M1 to anti-inflammatory M2 of KCs and inhibiting the proliferation of HSCs. Importantly, efficacy and recurrence prevention of chemogene therapy earlier in the liver fibrosis will be more effective than the treatment at later stage. In conclusion, this work proposes a novel strategy to improve the efficacy and prevent recurrence of liver fibrosis by dual-regulating of KCs and HSCs, and emphasizes the importance of therapy earlier in the treatment of liver fibrosis.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120311DOI Listing
December 2020

Role of platelet biomarkers in inflammatory response.

Biomark Res 2020 2;8:28. Epub 2020 Aug 2.

Department of Cardiology, Huashan Hospital, Fudan University, No.12 Middle Wulumuqi Road, Jing'an District, Shanghai, 200040 China.

Beyond hemostasis, thrombosis and wound healing, it is becoming increasingly clear that platelets play an integral role in inflammatory response and immune regulation. Platelets recognize pathogenic microorganisms and secrete various immunoregulatory cytokines and chemokines, thus facilitating a variety of immune effects and regulatory functions. In this review, we discuss recent advances in signaling of platelet activation-related biomarkers in inflammatory settings and application prospects to apply for disease diagnosis and treatment.
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http://dx.doi.org/10.1186/s40364-020-00207-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397646PMC
August 2020

Deaths from total and premature cardiovascular disease associated with high normal blood pressure and hypertension in rural Chinese men and elderly people.

J Hum Hypertens 2021 Aug 20;35(8):741-750. Epub 2020 Jul 20.

The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.

To investigate the association of blood pressure (BP) categories with total and premature cardiovascular disease (CVD) mortality in rural Chinese. The study included 14,539 adults ≥18 years in rural China. Baseline study visits were conducted in 2007-2008, and follow-up visits in 2013-2014. Data were collected by face-to-face questionnaire interview, and anthropometric and laboratory measurements. A sub-distribution hazards model was used to calculate adjusted sub-distribution hazard ratios (aSHRs) and 95% confidence intervals (CIs). During the 6-year follow-up, 257 total and 209 premature CVD deaths occurred. As compared with normal BP (systolic BP/diastolic BP (SBP/DBP) < 120/80 mmHg), for men and people aged ≥60 years, hypertension (SBP/DBP ≥ 140/90 mmHg) associated with total CVD mortality (aSHR 3.57, 95% CI 2.06-6.17; aSHR 2.15, 1.29-3.56) and premature CVD mortality (aSHR 4.41, 2.37-8.21; aSHR 2.31, 1.27-4.19). Also, as compared with normal BP, for men and people aged ≥60 years with high normal BP (SBP/DBP 120-139/80-89 mmHg), risk of total CVD mortality increased (aSHR 1.85, 1.05-3.28; aSHR 1.78, 1.05-3.04), as was premature CVD mortality (aSHR 1.89, 0.99-3.64; aSHR 1.91, 1.03-3.54). Among men and people aged ≥60 years in rural China, risk of total and premature CVD mortality was increased for those with high normal BP and hypertension. Prevention and treatment strategies for additional CVD risk reduction targeting men and elderly people with hypertension or even high normal BP are needed to reduce CVD mortality risk.
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http://dx.doi.org/10.1038/s41371-020-0379-4DOI Listing
August 2021

Pravastatin attenuates atherosclerosis after myocardial infarction by inhibiting inflammatory Ly6C monocytosis in apolipoprotein E knockout mice.

J Int Med Res 2020 Jul;48(7):300060520932816

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

Objective: To evaluate the protective effect of pravastatin on atherosclerotic development and inflammatory monocyte subset in atherosclerotic apolipoprotein E (ApoE) mice after myocardial infarction (MI).

Methods: Male ApoE mice (8 weeks old) were fed a high-fat diet for 14 weeks throughout the experiment. A MI model was produced using 18-week-old ApoE mice. They were randomly divided into three groups: sham group, MI group, and MI+Pra group (40 mg/kg/day pravastatin). After 4 weeks (at the end of the study period), the mice were sacrificed and cardiac function was evaluated by echocardiography. Aortic lesion areas were evaluated using oil red O staining. Plaque macrophage in aortic sinus was analyzed by immunofluorescence staining. Flow cytometry was used to explore the proportions of monocyte subsets in the blood, spleen, and bone marrow..

Results: Pravastatin improved cardiac function and reduced lesion areas. It also attenuated the supply of monocytes in spleen, especially the inflammatory Ly6C monocyte subset. Pravastatin also subsequently reduced macrophage accumulation in atherosclerotic lesions.

Conclusions: MI accelerated chronic atherosclerosis progress. Pravastatin suppressed atherosclerotic development and inhibited inflammatory monocytosis after MI in ApoE mice.
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http://dx.doi.org/10.1177/0300060520932816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361503PMC
July 2020

A stricter control of low-density lipoprotein is necessary for thrombosis reduction in "lower thrombosis risk" patients with atrial fibrillation: a multicenter retrospective cohort study.

J Thromb Thrombolysis 2020 Nov;50(4):849-857

Department of Cardiology, Huashan Hospital Fudan University, 12 Wulumuqizhong Road, Shanghai, 200040, China.

Patients with atrial fibrillation (AF) are associated with increased thrombotic events. Our previous case-control study showed low-density lipoprotein cholesterol (LDL-C) was an independent predictor of ischemic stroke in AF patients. To investigate the risks of thrombosis in relation to LDL-C among AF patients at different stroke risks by long-time follow-up. Atrial fibrillation patients without history of thrombosis enrolled from five hospitals were classified into low-risk (LR) and high-risk (HR) group according to CHADSVASc score and followed up with a median period of 26 months. Univariate and multivariate logistic regression analysis were performed in each group. The best cut-off value calculated by receiver operating characteristic (ROC) analysis was used to divide patients into low LDL-C (L-LDL) and high LDL-C (H-LDL) subgroups. Propensity score matching (PSM) and inverse probability of treatment weighted (IPTW) were utilized in both subgroups, after which Kaplan-Meier curves for thrombosis were performed. Univariate and multivariate analysis showed LDL-C was significantly related to thrombosis in LR, but less significantly in HR group. The best cut-off value was 2.155 mmol/L in LR and 2.795 mmol/L in HR group. Lower LDL-C was associated with decreased thrombosis in both groups by PSM and IPTW. Kaplan-Meier curves displayed that H-LDL subgroup was at higher thrombosis risk with significant difference at 24th month in LR patients. LDL-C independently predicts thrombosis with different cut-off values in AF patients at different risks. A stricter control of LDL-C level is necessary for thrombosis reduction in patients with lower score.
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http://dx.doi.org/10.1007/s11239-020-02110-xDOI Listing
November 2020

Combined Hydrophobization of Polyethylenimine with Cholesterol and Perfluorobutyrate Improves siRNA Delivery.

Bioconjug Chem 2020 03 22;31(3):698-707. Epub 2020 Jan 22.

Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Polyethylenimine (PEI) is a promising delivery vector of nucleic acids, but cytotoxicity and only moderate transfection efficacy with small RNAs limit its applications. Here we hypothesized that hydrophobization of PEI by combined modification with perfluorinated moieties (F) and cholesterol (Ch) will help in addressing both the cytotoxicity and siRNA delivery efficacy. To test the hypothesis, we synthesized a series of copolymers (F-PEI-Ch) by modifying PEI by reaction with heptafluorobutyric anhydride and cholesteryl chloroformate. We investigated and compared the effect of the modifications on siRNA delivery in vitro and in vivo. We found that the F-PEI-Ch copolymers assembled into micellar structures and that the copolymer with the highest Ch content exhibited the best siRNA delivery performance, including lower cytotoxicity, enhanced cell uptake, improved endosomal escape, and the best siRNA silencing efficacy in vitro and in vivo when compared with control PEI, F-PEI, and PEI-Ch. Overall, hydrophobization of PEI with a combination of cholesterol and superhydrophobic perfluorinated moieties represents a promising approach to the design of siRNA delivery vectors with decreased toxicity and enhanced transfection efficacy.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00834DOI Listing
March 2020

Cryoballoon ablation for atrial tachycardia resulting from fibrillatory activity in superior vena cava and multilevel exit block.

J Cardiovasc Electrophysiol 2020 02 15;31(2):557-559. Epub 2020 Jan 15.

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

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http://dx.doi.org/10.1111/jce.14325DOI Listing
February 2020

Factors influencing cognitive function in patients with atrial fibrillation: a cross-sectional clinical study.

J Int Med Res 2019 Dec 23;47(12):6041-6052. Epub 2019 Oct 23.

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

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http://dx.doi.org/10.1177/0300060519882556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045671PMC
December 2019

Oral anticoagulant prescribing in elderly patients above and below age 80 with atrial fibrillation
.

Int J Clin Pharmacol Ther 2019 Sep;57(9):458-463

Background: Oral anticoagulation is efficient to prevent ischemic stroke in atrial fibrillation (AF), but in very old patients, physicians always remain cautious to use anticoagulants concerning the bleeding risk. This research aims to investigate the current situation of oral anticoagulation therapy in very old (≥ 80 years) AF patients.

Materials And Methods: We carried out a cross-sectional study in an urban area in China from 2014 to 2016. Characteristics of the very old patients (age ≥ 80 years) and the younger patients (age < 80 years) were compared. Logistic analysis was used to estimate the association between oral anticoagulation therapy and CHADS-VASc score.

Results: A total of 1,000 AF patients were enrolled; 306 were very old patients, and 694 were younger patients. In the very old group, 48.0% were women, and the average age was 84.12 ± 3.62 years. In the younger group, 35.3% were women, and the average age was 66.92 ± 9.02 years. CHADS-VASc score was 2.8 ± 1.7 in the younger group and 4.5 ± 1.5 in the very old group (p < 0.001). The proportion of oral anticoagulation was low in patients with AF (31.8%) and even lower in very old patients compared to younger patients (24.5 vs. 35.0%, p = 0.004). Moreover, oral anticoagulation therapy was strongly associated with CHADS-VASc scores only in the younger group, but not in the very old group, which means the very old patients were not treated with oral anticoagulation according to their elevated CHADS-VASc scores.

Conclusion: Anticoagulants were underused in AF patients, particularly in very old patients. Evidence is accumulating that the very old patients could still benefit from anticoagulants so that physicians should not exclude such patients from anticoagulation only because of their older age.
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http://dx.doi.org/10.5414/CP203502DOI Listing
September 2019

Association of serum cystatin C levels with acute coronary syndrome in patients of advanced age.

J Int Med Res 2019 May 14;47(5):1987-1997. Epub 2019 Mar 14.

Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Objective: This study was performed to investigate the relationship between the serum cystatin C (Cys C) level and acute coronary syndrome (ACS) in patients of advanced age.

Methods: The study included 184 patients with ACS and 46 healthy control subjects. Statistical analysis was performed using SPSS version 14.0 (SPSS Inc., Chicago, IL, USA).

Results: The serum Cys C level was significantly higher in patients with than without ACS (1.24 ± 0.30 vs. 1.42 ± 0.46 mg/L, respectively). Patients with more stenotic coronary arteries were significantly more likely to have higher median serum Cys C and creatinine levels and a lower estimated glomerular filtration rate. The multivariate logistic regression analysis demonstrated that the serum Cys C level was independently associated with the presence of ACS and the quantity of stenotic coronary arteries after adjustment for confounding factors. Additionally, the serum Cys C level was positively correlated with age, the creatinine level, and the N-terminal pro-B-type natriuretic peptide level in all patients but was negatively correlated with the estimated glomerular filtration rate.

Conclusion: A high serum Cys C level was independently associated with ACS and the quantity of stenotic coronary arteries in patients of advanced age regardless of renal function.
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http://dx.doi.org/10.1177/0300060519833576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567780PMC
May 2019

Exosomes derived from miR-146a-modified adipose-derived stem cells attenuate acute myocardial infarction-induced myocardial damage via downregulation of early growth response factor 1.

J Cell Biochem 2019 03 26;120(3):4433-4443. Epub 2018 Oct 26.

Department of Cardiovascular Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, China.

Multiple studies demonstrated that early growth response factor 1 (EGR1) induces myocardial damage after acute myocardial infarction (AMI). Recent evidence indicates that microRNAs (miRNA) play an important role in exosome-mediated cardioprotection after AMI. Bioinformatics analysis has shown that miR-146a can regulate the expression of EGR1, so the aim of this study was to determine if miR-146a plays a role in exosome-mediated cardioprotection by regulation of EGR1 after AMI. Exosomes were isolated from wild- or miR-146a-modified adipose-derived stem cells (ADSCs), and the therapeutic effect of exosomes was assessed in an AMI model in rats and hypoxic-induced H9c2 model cells. The results showed that miR-146a containing exosomes had more effect than the exosome treatment group on the suppression of AMI-induced apoptosis, inflammatory response, and fibrosis in an AMI rat model. Both in vivo and in vitro experiments found that miR-146a interacted with the 3'-untranslated region of EGR1 and suppressed posttranscriptional EGR1 expression, which was confirmed by the luciferase reporter assay. We also found that suppressed EGR1 expression reversed AMI or hypoxia-induced TLR4/NFκB signal activation, which played an important role in the promotion of myocardial cell apoptosis, inflammatory response, and fibrosis. Taken together, these findings suggested that exosomes derived from miR-146a-modified ADSCs attenuated AMI-induced myocardial damage via downregulation of EGR1.
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http://dx.doi.org/10.1002/jcb.27731DOI Listing
March 2019

Association of hypertension with parity and with the interaction between parity and body mass index in rural Chinese women.

J Am Soc Hypertens 2018 11 19;12(11):789-797. Epub 2018 Sep 19.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. Electronic address:

A cross-sectional study was conducted; information for 9247 women living in rural China was collected by questionnaire interview and anthropometric and laboratory measurements during July to August 2013 and July to October 2014. Multiple logistic regression analysis was used to examine the association between parity and hypertension, estimating odds ratios and 95% confidence intervals (CIs). The biological interaction between parity and body mass index was estimated by the relative excess risk due to interaction, attributable proportion due to the interaction, and synergy index. In our study, the prevalence of multiparity and hypertension was 93.10% and 22.90% in premenopausal women and 98.04% and 51.06% in postmenopausal women, respectively. For premenopausal women, parity hypertension was not associated with hypertension. And for postmenopausal women, as compared with para 0-1 status, para 2, 3, 4, and ≥ 5 were positively associated with hypertension: adjusted odds ratios (95% CI) was 2.04 (1.24-3.38), 2.25 (1.32-3.82), 2.41 (1.34-4.36), and 2.10 (1.04-4.22), respectively. The interaction effect between multiparity and overweight/obesity on hypertension was additive (relative excess risk due to interaction [95% CI]: 1.59, 0.19-3.00; attributable proportion due to the interaction [95% CI]: 0.34, 0.02-0.67) only in postmenopausal women. Parity was independently related to hypertension, and the interaction effect between multiparity and overweight/obesity on hypertension was additive in rural postmenopausal women.
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http://dx.doi.org/10.1016/j.jash.2018.09.005DOI Listing
November 2018

Identification of an obesity index for predicting metabolic syndrome by gender: the rural Chinese cohort study.

BMC Endocr Disord 2018 Aug 6;18(1):54. Epub 2018 Aug 6.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Background: To compare the accuracy of different obesity indexes, including waist circumference (WC), weight-to-height ratio (WHtR), body mass index (BMI), and lipid accumulation product (LAP), in predicting metabolic syndrome (MetS) and to estimate the optimal cutoffs of these indexes in a rural Chinese adult population.

Methods: This prospective cohort involved 8468 participants who were followed up for 6 years. MetS was defined by the International Diabetes Federation, American Heart Association, and National Heart, Lung, and Blood Institute criteria. The power of the 4 indexes for predicting MetS was estimated by receiver operating characteristic (ROC) curve analysis and optimal cutoffs were determined by the maximum of Youden's index.

Results: As compared with WHtR, BMI, and LAP, WC had the largest area under the ROC curve (AUC) for predicting MetS after adjusting for age, smoking, drinking, physical activity, and education level. The AUCs (95% CIs) for WC, WHtR, BMI, and LAP for men and women were 0.862 (0.851-0.873) and 0.806 (0.794-0.817), 0.832 (0.820-0.843) and 0.789 (0.777-0.801), 0.824 (0.812-0.835) and 0.790 (0.778-0.802), and 0.798 (0.785-0.810) and 0.771 (0.759-0.784), respectively. The optimal cutoffs of WC for men and women were 83.30 and 76.80 cm. Those of WHtR, BMI, and LAP were approximately 0.51 and 0.50, 23.90 and 23.00 kg/m, and 19.23 and 20.48 cm.mmol/L, respectively.

Conclusions: WC as a preferred index over WHtR, BMI, and LAP for predicting MetS in rural Chinese adults of both genders; the optimal cutoffs for men and women were 83.30 and 76.80 cm.
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http://dx.doi.org/10.1186/s12902-018-0281-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090693PMC
August 2018

A multifunctional ternary Cu(II)-carboxylate coordination polymeric nanocomplex for cancer thermochemotherapy.

Int J Pharm 2018 Oct 2;549(1-2):1-12. Epub 2018 Jul 2.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China. Electronic address:

Metal-based photothermal therapy has been widely used in the biomedicine field and includes gold nanoparticles, silver nanoparticles and copper sulfide nanoparticles. Furthermore, the coordination bonding-based metal nanocomplex is a new generation of photothermal agents for cancer therapy due to its high photothermal transduction efficiency, good biocompatibility, biodegradation and bioactivity. In this study, we designed a coordination bonding-based copper (Cu(II))-carboxylate ternary architecture, which consists of a conjugate dopamine-modified nontoxic hyaluronic acid, copper ions and citric acid. When the Cu(II) coordinated with the carboxyl groups, the splitting d orbitals energy gap of Cu(II) and the capability of electron transition were enhanced, which can increase the extinction ability in the near-infrared region for enhancing photothermal therapy. Moreover, the degradation of hyaluronic acid by hyaluronidase highly expressed in the tumor microenvironment led to the release of Cu-citric acid complexes, thus exhibiting an additional chemotherapeutic effect. The nanocomplexes possessed high-performance photothermal conversion, determined to be 21.3%. The solution could be easily heated to above 42 °C, which was sufficient to ablate the cancer cells. An obvious decrease in cell viability was observed in B16F10 cells incubated with the nanocomplexes under laser at the lower concentration of 20 μg/mL Cu(II). Upon near-infrared laser irradiation, the nanocomplexes showed high photothermal therapy and chemotherapeutic efficacy for breast cancer in vivo. This study demonstrated that the Cu(II)-carboxylate coordination nanocomplex is a promising new effective and facilely prepared thermochemotherapy agent for combination therapy against cancer.
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http://dx.doi.org/10.1016/j.ijpharm.2018.06.048DOI Listing
October 2018

TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance.

Oxid Med Cell Longev 2018 26;2018:3181278. Epub 2018 Jun 26.

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

Mitochondrial dynamic imbalance associates with several cardiovascular diseases. However, the role of mitochondrial dynamics in TLR4 activation-mediated dilated cardiomyopathy (DCM) progress remains unknown. A model of experimental autoimmune myocarditis (EAM) was established in BALB/c mice on which TLR4 activation by LPS-EB or TLR4 inhibition by LPS-RS was performed to induce chronic inflammation for 5 weeks. TLR4 activation promoted the transition of EAM to DCM as demonstrated by increased cardiomyocyte apoptosis, myocardial fibrosis, ventricular dilatation, and declined heart function. TLR4 inhibition mitigated the above DCM changes. Transmission electron microscope study showed that mitochondria became fragmented, also with damaged crista in ultrastructure in EAM mice. TLR4 activation aggravated the above mitochondrial aberration, and TLR4 inhibition alleviated it. The mitochondrial dynamic imbalance and damage in DCM development were mainly associated with OPA1 downregulation, which may be caused by elevated TNF- level and ROS stress after TLR4 activation. Furthermore, OMA1/YME1L abnormal degradation was involved in the OPA1 dysfunction, and intervening OMA1/YME1L in H9C2 significantly alleviated mitochondrial fission, ultrastructure damage, and cell apoptosis induced by TNF- and ROS. These data indicate that TLR4 activation resulted in OPA1 dysfunction, promoting mitochondrial dynamic imbalance and damage, which may involve in the progress of EAM to DCM.
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http://dx.doi.org/10.1155/2018/3181278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038665PMC
October 2018

Tenascin C: A Potential Biomarker for Predicting the Severity of Coronary Atherosclerosis.

J Atheroscler Thromb 2019 Jan 17;26(1):31-38. Epub 2018 May 17.

Department of Cardiology, Huashan Hospital, Fudan University.

Aims: Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide and one of the greatest threats to public health. Tenascin C (TNC) is an extracellular matrix glycoprotein that is found in low concentrations in normal tissues and is enhanced by a range of cardiovascular pathologies. This study aimed to evaluate the value of TNC in assessing the severity of atherosclerosis measured by the Gensini score.

Methods: A total of 157 patients with chest pains who underwent selective coronary angiography for suspected coronary atherosclerosis were enrolled. The patients were divided into the CAD group and non-CAD group according to symptoms and angiography. Demographic data and laboratory analyses were collected.

Results: The mean TNC level was significantly higher in the CAD group than in the non-CAD group (p<0.001). A significant positive correlation between TNC levels and Gensini score (p<0.01, r=0.672) was found. ROC curve analysis demonstrated that the cutoff value for TNC at 89.48 ng/mL was well differentiated in the CAD and non-CAD groups. Furthermore, TNC was also a good predictor for a higher Gensini score (the third tertile) in the ROC curve analysis. When the cutoff was accepted as 100.91 ng/mL, the sensitivity and specificity were 82.7% and 79%, respectively.

Conclusion: A significant relationship was found between the Gensini score and serum TNC level. TNC levels can be considered in risk assessments for CAD before angiography.
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http://dx.doi.org/10.5551/jat.42887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308263PMC
January 2019

Response by Hu et al to Letters Regarding Article, "Platelets Express Activated P2Y Receptor in Patients With Diabetes Mellitus".

Circulation 2018 04;137(17):1877-1878

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, People's Republic of China (L.H., S.Z., Z.D.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032709DOI Listing
April 2018

Cohort study to determine the waist circumference cutoffs for predicting type 2 diabetes mellitus in rural China.

Diabetes Metab Res Rev 2018 09 4;34(6):e3007. Epub 2018 May 4.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Background: Limited information is available on the cutoffs of waist circumference (WC) for predicting type 2 diabetes mellitus (T2DM). We aimed to define the optimal WC cutoffs for predicting T2DM among rural Chinese people.

Methods: A cohort of 11 968 participants (732 new-onset T2DM) from a rural area in China with age 18 to 87 years was established at baseline during July to August of 2007 and 2008 and followed up during July to August of 2013 and 2014. Scatterplot, X-tile plot, and receiver operating characteristic (ROC) curve analyses were used to determine WC cutoffs for predicting T2DM.

Results: The WC cutoffs for males and females were 84 and 86 cm (scatterplot), 83 and 88 cm (X-tile plot), and 87 and 88 cm (ROC curve). According to the highest risk score, the optimal WC cutoffs were 87 cm for males and 88 cm for females. With the optimal WC cutoffs, the sensitivity, specificity, positive likelihood ratio, area under the ROC curve, and population-attributable risk proportions were 67.9%, 67.0%, 2.06%, 0.70%, and 46%, respectively, for males and 52.5%, 75.0%, 2.10%, 0.69%, and 34%, respectively, for females; the corresponding adjusted hazard ratio for WC predicting T2DM was 3.66 (95% confidence interval 2.80-4.78) for males and 2.55 (2.08-3.12) for females.

Conclusions: The optimal WC cutoffs for predicting T2DM were similar between males and females. As well, the criteria of WC for central obesity are no longer practical for predicting T2DM.
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http://dx.doi.org/10.1002/dmrr.3007DOI Listing
September 2018

Comparison of body mass index, waist circumference, conicity index, and waist-to-height ratio for predicting incidence of hypertension: the rural Chinese cohort study.

J Hum Hypertens 2018 03 7;32(3):228-235. Epub 2018 Feb 7.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

This study compared the ability of body mass index (BMI), waist circumference (WC), conicity index, and waist-to-height ratio (WHtR) to predict incident hypertension and to identify the cutoffs of obesity indices for predicting hypertension in rural Chinese adults. This prospective cohort study recruited 9905 participants aged 18-70 years during a median follow-up of 6 years in rural China. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to assess the association, predictive ability, and optimal cutoffs (in terms of hypertension risk factors) of the four obesity indices: BMI, WC, conicity index, and WHtR. The 6-year cumulative incidence of hypertension was 19.89% for men and 18.68% for women, with a significant upward trend of increased incident hypertension with increasing BMI, WC, conicity index, and WHtR (P for trend < 0.001) for both men and women. BMI and WHtR had the largest area under the ROC curve for identifying hypertension for both genders. The optimal cutoff values for BMI, WC, conicity index, and WHtR for predicting hypertension were 22.65 kg/m, 82.70 cm, 1.20, and 0.49, respectively, for men, and 23.80 kg/m, 82.17 cm, 1.20, and 0.52, respectively, for women. BMI, WC, conicity index, and WHtR cutoffs may offer a simple and effective way to screen hypertension in rural Chinese adults. BMI and WHtR were superior to WC and conicity index for predicting incident hypertension for both genders.
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http://dx.doi.org/10.1038/s41371-018-0033-6DOI Listing
March 2018

Pharmacological inhibition of S6K1 facilitates platelet activation by enhancing Akt phosphorylation.

Platelets 2019 19;30(2):241-250. Epub 2017 Dec 19.

a Department of Cardiology , Huashan Hospital, Fudan University , Shanghai , China.

Platelet activation and thrombus formation is a delicate process involving a series of crosstalk between different pathways. P70 ribosomal S6 kinase1 (S6K1) is a member of serine/threonine kinases and can be phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1). S6K1 is widely reported to play important roles in cancers and metabolic diseases, but the role of S6K1 and the importance of phosphorylation on Thr229 in platelet activation have not been defined. PF-4708671 is a recently synthesized highly specific inhibitor of S6K1. In this study, we tested PF-4708671 to assess the role of S6K1 in platelet. PF-4708671 facilitated mouse and human platelet aggregation and ATP secretion induced by collagen, thrombin, and adenosine diphosphate through enhanced Akt and Gsk3β phosphorylation. PF-4708671 also accelerated integrin αIIbβ3-mediated clot retraction and spreading. Intravenously given PF-4708671 shortened the occlusion time in arterial thrombosis model. Further results demonstrated that S6K1 was phosphorylated by PDK1 on Thr229 in the resting platelets and dephosphorylated in response to agonist stimulation. PDK1-deficient mice showed higher aggregation when PI3K-Akt-Gsk3β signaling was blocked by the Gsk3β-inhibitor SB216763. Thus, S6K1 Thr229 phosphorylation might function as a regulator that prevents platelets from activation. S6K1 inhibition may yield potential pro-thrombotic effects and should be used cautiously when considered as a therapy.
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http://dx.doi.org/10.1080/09537104.2017.1416075DOI Listing
April 2019
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