Publications by authors named "Xinye Li"

45 Publications

Gut microbiota-derived short-chain fatty acids and hypertension: Mechanism and treatment.

Biomed Pharmacother 2020 Oct 18;130:110503. Epub 2020 Aug 18.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address:

Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.
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http://dx.doi.org/10.1016/j.biopha.2020.110503DOI Listing
October 2020

A novel nomogram with preferable capability in predicting the overall survival of patients after radical esophageal cancer resection based on accessible clinical indicators: A comparison with AJCC staging.

Cancer Med 2021 07 15;10(13):4228-4239. Epub 2021 Jun 15.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Esophageal cancer (EC) is a malignant tumor with high mortality. Nomogram is an important tool used in clinical prognostic assessment. We aimed to establish a novel nomogram to predict the overall survival (OS) of EC patients after radical esophagectomy.

Methods: Data pertaining to the survival, demography, and clinicopathology of 311 EC patients who underwent radical esophagectomy were retrospectively investigated. The nomogram was established based on Cox hazard regression analysis. The calibration curves and Harrell's concordance index (C-index) were used to verify the predictive accuracy and ROC curves were used to assess the efficacy of the nomogram. Kaplan-Meier curves showed the prognostic value of the related risk classification system. Pearson correlation test was performed to determine the correlation between the risk classification system and TNM staging.

Results: The median OS and 5-year survival rates in the primary and validation cohorts were 44 months and 29.8%, and 52 months and 27.1%, respectively. We used six independent prognostic factors-age, Sex, AGR, PRL, N stage, and PNI-in the nomogram. The C-index of nomogram was 0.75 and 0.70 in the primary and validation cohorts, respectively. Calibration curves indicated high consistency between actual and predicted OS. ROC curves showed that nomogram has a better efficacy compared with TNM staging in both cohorts. Patients were divided into three risk groups according to the total nomogram score, the median OS in each group was significantly different in both cohorts. Furthermore, the risk classification system was strongly correlated with the T and N staging system and exhibited a better OS prediction capability.

Conclusions: We established a novel and practical nomogram with a subordinate risk classification system to predict the OS of patients after radical esophagectomy. Compared with AJCC staging, this nomogram had preferable clinical capability in terms of individual prognosis assessment.
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http://dx.doi.org/10.1002/cam4.3878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267131PMC
July 2021

Exploration of the potential mechanism of Banxia Xiexin Decoction for the effects on TNBS-induced ulcerative colitis rats with the assistance of network pharmacology analysis.

J Ethnopharmacol 2021 Sep 15;277:114197. Epub 2021 May 15.

Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Ethnopharmacological Relevance: Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant.

Aim Of The Study: This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research.

Methods: Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the "herbs-components-targets-disease" network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out.

Results: The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.
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http://dx.doi.org/10.1016/j.jep.2021.114197DOI Listing
September 2021

Dietary Fibre Intake in Type 2 and New-Onset Prediabetes/Diabetes after Acute Pancreatitis: A Nested Cross-Sectional Study.

Nutrients 2021 Mar 29;13(4). Epub 2021 Mar 29.

School of Medicine, University of Auckland, Auckland 1023, New Zealand.

The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (β = -0.154, = 0.006), insoluble fibre (β = -0.133, = 0.01), and soluble fibre (β = -0.13, = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (β = -0.069, = 0.004) and nuts (β = -0.039, = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (β = -0.054, = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.
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http://dx.doi.org/10.3390/nu13041112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066410PMC
March 2021

Usefulness of Rhythm Monitoring Following Acute Ischemic Stroke.

Am J Cardiol 2021 05 20;147:44-51. Epub 2021 Feb 20.

Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

We characterized monitor utilization in stroke survivors and assessed associations with underlying clinical atrial fibrillation (AF) risk. We retrospectively analyzed consecutive patients with acute ischemic stroke 10/2018-6/2019 without prevalent AF and assessed the 6-month incidence of monitor utilization (Holter/ECG, event/patch, implantable loop recorder [ILR]) using Fine-Gray models accounting for the competing risk of death. We assessed for predictors of monitor utilization using cause-specific hazards regression adjusted for the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score, stroke subtype, and discharge disposition. Of 493 patients with acute ischemic stroke (age 65±16; 47% women), the 6-month incidence of monitor utilization was 36.5% (95% CI 31.7, 41.3), and 6-month mortality was 13.6% (10.4, 16.8). Monitoring was performed with Holter/event (n = 107; 72.3%), ILR (n = 34; 23.0%) or both (n = 7; 4.7%). Monitoring was more likely after cryptogenic (hazard ratio [HR] 4.53 [3.22, 6.39]; 6-month monitor incidence 70.6%) and cardioembolic (HR 2.43 [1.28, 4.62]; incidence 47.7%) stroke, versus other/undocumented (incidence 22.7%). Among patients with cryptogenic stroke, the 6-month incidence of ILR was 27.5% [18.5, 36.5]. Monitoring was more likely after discharge home (HR 1.80 [1.29, 2.52]; incidence 46.1%) versus facility (incidence 24.9%). Monitoring was not associated with CHARGE-AF score (HR 1.08 per 1-SD increase [0.91, 1.27]), even though CHARGE-AF was associated with incident AF (HR 1.56 [1.03, 2.35]). In conclusion, rhythm monitors are utilized after one-third of ischemic strokes. Monitoring is more frequent after cryptogenic strokes, though ILR use is low. Monitor utilization is not associated with AF risk.
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http://dx.doi.org/10.1016/j.amjcard.2021.01.038DOI Listing
May 2021

Dietary carbohydrate intake and insulin traits in individuals after acute pancreatitis: Effect modification by intra-pancreatic fat deposition.

Pancreatology 2021 Mar 2;21(2):353-362. Epub 2021 Feb 2.

School of Medicine, University of Auckland, Auckland, New Zealand. Electronic address:

Objectives: Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD).

Methods: All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-β were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis).

Results: The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-β in both the unadjusted (p < 0.001 both) and fully adjusted models (p < 0.001 both); and with HOMA-IR in the fully adjusted model (p < 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-β (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group).

Conclusions: Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.
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http://dx.doi.org/10.1016/j.pan.2021.01.018DOI Listing
March 2021

Determination of Synthetic Colorants in Beverages by Deep Eutectic Solvent-Based Effervescence-Assisted Dispersive Liquid-Liquid Microextraction Coupled with High-Performance Liquid Chromatography.

J Chromatogr Sci 2021 Feb 3. Epub 2021 Feb 3.

Department of Chemistry, College of Chemistry and Environmental Science, Hebei University; Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002, China.

In this paper, a deep eutectic solvent (DES)-based effervescence-assisted dispersive liquid-liquid microextraction method was proposed for the determination of four synthetic colorants in beverages by high-performance liquid chromatography. In this method, DES synthesized from choline chloride and phenol was used as extractant. The dispersion of DES was assisted by in situ CO2 produced from the effervescence reaction between NaH2PO4 and Na2CO3 without using any organic solvent or auxiliary equipment. Furthermore, phase separation occurred naturally in the presence of the salt products of effervescence reaction, without the addition of any other salting out reagents. Some important parameters, such as species, molar ratio and volume of DES, composition and amount of effervescent agents, were optimized to achieve the best extraction efficiency. Under the optimal conditions, extraction recoveries were obtained for the analytes in the range of 83.5-114.8%. The limits of detection were in the range of 0.6-3.0 ng/mL. Relative standard deviations for intra- and interday precision were <4.68 and 6.08%, respectively. This simple, rapid, cost-effective and environmentally friendly method has been successfully applied to the analysis of synthetic colorants in 10 kinds of beverage samples.
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http://dx.doi.org/10.1093/chromsci/bmab002DOI Listing
February 2021

Bifurcation Analysis of a Micro-Machined Gyroscope with Nonlinear Stiffness and Electrostatic Forces.

Micromachines (Basel) 2021 Jan 22;12(2). Epub 2021 Jan 22.

School of Automobile and Transportation, Tianjin University of Technology and Education, Tianjin 300222, China.

The bifurcation of the periodic response of a micro-machined gyroscope with cubic supporting stiffness and fractional electrostatic forces is investigated. The pull-in phenomenon is analyzed to show that the system can have a stable periodic response when the detecting voltage is kept within a certain range. The method of averaging and the residue theorem are employed to give the averaging equations for the case of primary resonance and 1:1 internal resonance. Transition sets on the driving/detecting voltage plane that divide the parameter plane into 12 persistent regions and the corresponding bifurcation diagrams are obtained via the singularity theory. The results show that multiple solutions of the resonance curves appear with a large driving voltage and a small detecting voltage, which may lead to an uncertain output of the gyroscope. The effects of driving and detecting voltages on mechanical sensitivity and nonlinearity are analyzed for three persistent regions considering the operation requirements of the micro-machined gyroscope. The results indicate that in the region with a small driving voltage, the mechanical sensitivity is much smaller. In the other two regions, the variations in the mechanical sensitivity and nonlinearity are analogous. It is possible that the system has a maximum mechanical sensitivity and minimum nonlinearity for an appropriate range of detecting voltages.
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http://dx.doi.org/10.3390/mi12020107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910899PMC
January 2021

Association between Habitual Dietary Iron Intake and Glucose Metabolism in Individuals after Acute Pancreatitis.

Nutrients 2020 Nov 22;12(11). Epub 2020 Nov 22.

School of Medicine, University of Auckland, Auckland 1023, New Zealand.

Dietary intake of iron is known to be associated with impaired glucose metabolism. However, its involvement in derangements of glucose metabolism after acute pancreatitis (AP) is not completely understood. The aim was to investigate the association between dietary iron intake and markers of glucose metabolism in individuals after an attack of AP. Fasting blood samples were collected to analyse markers of glucose metabolism (fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)). The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of dietary iron (total, haem, and non-haem). Multivariable linear regression analyses were conducted and six statistical models were built to adjust for covariates. A total of 109 individuals after AP were studied in a cross-sectional fashion. Total iron (β (95% confidence interval) = -0.19 (-0.35, -0.05); = 0.01 in the most adjusted model) and non-haem iron (β (95% confidence interval) = -0.19 (-0.33, -0.04); = 0.03 in the most adjusted model) were significantly associated with FPG, consistently in all adjusted model. Total iron and non-haem iron did not have consistent significant associations with HbA1c. Dietary haem iron intake was not associated with either FPG or HbA1c. Habitual intake of dietary iron is inversely associated with FPG in individuals after an attack of AP and may be involved in the pathogenesis of new-onset diabetes after pancreatitis. Prospective longitudinal studies are now warranted to unveil the specific mechanism underlying the involvement of dietary iron.
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http://dx.doi.org/10.3390/nu12113579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700518PMC
November 2020

Nanocomposites with Three-Dimensional Architecture and Impact on Photovoltaic Effect.

Nano Lett 2020 Dec 30;20(12):8789-8795. Epub 2020 Nov 30.

Zentrum für Innovationskompetenz SiLi-nano, Martin Luther Universität Halle-Wittenberg, Halle (Saale) 06120, Germany.

We demonstrate the synthesis of self-assembled three-dimensional nanocomposite thin films consisting of NiO nanocolumns in an layered Aurivillius phase matrix. The structures were grown on single-crystal SrTiO substrates via pulsed laser deposition (PLD) with single ceramic (PbTiO)(BiNiNbO) targets. The nanocolumns, which are about 10 nm in diameter each, extend over the entire film thickness of up to 225 nm. We reveal the difference in electrical conduction properties of the nanocolumns and the surrounding matrix on the nanoscale via conductive atomic force microscopy. The nanocomposite thin films exhibit improved photovoltaic performance compared to both pure PbTiO and homogeneous Aurivillius phase thin films.
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http://dx.doi.org/10.1021/acs.nanolett.0c03654DOI Listing
December 2020

Cardiac CaMKII and Wenxin Keli Prevents Ang II-Induced Cardiomyocyte Hypertrophy by Modulating CnA-NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells.

Evid Based Complement Alternat Med 2020 19;2020:9502651. Epub 2020 Oct 19.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing 100053, China.

Previous studies have demonstrated that calcium-/calmodulin-dependent protein kinase II (CaMKII) and calcineurin A-nuclear factor of activated T-cell (CnA-NFAT) signaling pathways play key roles in cardiac hypertrophy (CH). However, the interaction between CaMKII and CnA-NFAT signaling remains unclear. H9c2 cells were cultured and treated with angiotensin II (Ang II) with or without silenced CaMKII (siCaMKII) and cyclosporine A (CsA, a calcineurin inhibitor) and subsequently treated with Wenxin Keli (WXKL). Patch clamp recording was conducted to assess L-type Ca current (I), and the expression of proteins involved in signaling pathways was measured by western blotting. Myocardial cytoskeletal protein and nuclear translocation of target proteins were assessed by immunofluorescence. The results indicated that siCaMKII suppressed Ang II-induced CH, as evidenced by reduced cell surface area and I. Notably, siCaMKII inhibited Ang II-induced activation of CnA and NFATc4 nuclear transfer. Inflammatory signaling was inhibited by siCaMKII and WXKL. Interestingly, CsA inhibited CnA-NFAT pathway expression but activated CaMKII signaling. In conclusion, siCaMKII may improve CH, possibly by blocking CnA-NFAT and MyD88 signaling, and WXKL has a similar effect. These data suggest that inhibiting CaMKII, but not CnA, may be a promising approach to attenuate CH and arrhythmia progression.
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http://dx.doi.org/10.1155/2020/9502651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603598PMC
October 2020

Synthesis of the Se-HPCF composite a liquid-solution route and its stable cycling performance in Li-Se batteries.

Dalton Trans 2020 Oct;49(41):14536-14542

Engineering Research Center of Polymer Green Recycling of Ministry of Education, College of Environmental Science and Engineering, Fujian Normal University, Fuzhou, Fujian 350007, China. and Fujian Key Laboratory of Pollution Control & Resource Reuse, Fuzhou, Fujian 350007, China and Fuqing Branch of Fujian Normal University, Fuqing, Fujian 350300, China.

In pursuit of a one-dimensional (1D) porous carbon framework to restrain selenium for advanced lithium-selenium batteries, the Se-hierarchical porous carbon fiber composite (Se-HPCF) is synthesized via a liquid-solution route followed by calcination treatment. The unique architecture of the HPCF, which exhibits a large surface area and high pore volume, is fabricated using sodium lignosulfonate (LN) as a green pore-forming agent via electrospinning. As a cathode material for Li-Se batteries, the Se-HPCF composite exhibits superior electrochemical performance. A reversible capacity of 533 mA h g-1 is maintained at a rate of 0.2C after 50 cycles. In addition, the Se-HPCF composite delivers high rate performance with a high specific capacity of 351 mA h g-1 at 5C. The enhanced capacity retention and rate performance of Se-HPCF is generated by the 1D structure characteristics, and the liquid phase melting diffusion method could be applied to produce other related materials.
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http://dx.doi.org/10.1039/d0dt03035jDOI Listing
October 2020

Global Temperature Sensing for an Operating Power Transformer Based on Raman Scattering.

Sensors (Basel) 2020 Aug 30;20(17). Epub 2020 Aug 30.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Baoding 071003, China.

Traditional monitoring methods cannot obtain the overall thermal information for power transformers. To solve this problem, a distributed fiber optic sensor (DFOS) was creatively applied inside an operating 35 kV power transformer by highly integrating with the electromagnetic wires. Then, the transformer prototype with totally global sensing capability was successfully developed and it was qualified for power grid application through the strict ex-factory tests. The as designed optical fiber sensor works stably all the time with a temperature accuracy of ±0.2 °C and spatial positioning accuracy of 0.8 m. Based on the obtained internal temperature distribution, Gaussian convolution was further applied for the signal processing and hereby, the hotspots for all the windings and iron cores could be accurately traced. The hottest points were located at 89.1% (55 °C) of the high voltage winding height and 89.7% (77.5 °C) of the low voltage winding height. The actual precise hotspot location corrected the traditional cognition on the transformer windings and it would serve as an essential reference for the manufactures. This new nondestructive internal sensing and condition monitoring method also exhibits a promising future for the DFOS applying in the high-voltage electrical apparatus industry.
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http://dx.doi.org/10.3390/s20174903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506647PMC
August 2020

Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: a meta-analysis and systematic review.

Crit Care 2020 07 28;24(1):468. Epub 2020 Jul 28.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission.

Methods: Two investigators searched the PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), Wanfang, MedRxiv, and ChinaXiv databases for articles published through March 30, 2020. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. The data were extracted independently by two investigators.

Results: The analysis included 23 studies with 4631 total individuals. The proportions of severe disease, ICU admission, or death among patients with non-elevated TnI (or troponin T [TnT]), and those with elevated TnI (or TnT) were 12.0% and 64.5%, 11.8% and 56.0%, and 8.2% and. 59.3%, respectively. Patients with elevated TnI levels had significantly higher risks of severe disease, ICU admission, and death (RR 5.57, 95% CI 3.04 to 10.22, P < 0.001; RR 6.20, 95% CI 2.52 to 15.29, P < 0.001; RR 5.64, 95% CI 2.69 to 11.83, P < 0.001). Patients with an elevated CK level were at significantly increased risk of severe disease or ICU admission (RR 1.98, 95% CI 1.50 to 2.61, P < 0.001). Patients with elevated CK-MB levels were at a higher risk of developing severe disease or requiring ICU admission (RR 3.24, 95% CI 1.66 to 6.34, P = 0.001). Patients with newly occurring arrhythmias were at higher risk of developing severe disease or requiring ICU admission (RR 13.09, 95% CI 7.00 to 24.47, P < 0.001). An elevated IL-6 level was associated with a higher risk of developing severe disease, requiring ICU admission, or death.

Conclusions: COVID-19 patients with elevated TnI levels are at significantly higher risk of severe disease, ICU admission, and death. Elevated CK, CK-MB, LDH, and IL-6 levels and emerging arrhythmia are associated with the development of severe disease and need for ICU admission, and the mortality is significantly higher in patients with elevated LDH and IL-6 levels.
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http://dx.doi.org/10.1186/s13054-020-03183-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386170PMC
July 2020

Facile fabrication of a vanadium nitride/carbon fiber composite for half/full sodium-ion and potassium-ion batteries with long-term cycling performance.

Nanoscale 2020 May 6;12(19):10693-10702. Epub 2020 May 6.

Engineering Research Center of Polymer Green Recycling of Ministry of Education, College of Environmental Science and Engineering, Fujian Normal University, Fuzhou, Fujian 350007, China.

Vanadium-based composite anodes have been designed for applications in alkali metal ion batteries, including lithium-ion batteries (LIBs), sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). However, the problems of inferior long-term cycling stability caused by the large volume change and dissolution of vanadium-based active materials during cycles and slow diffusion for large radii of Na and K still limit their underlying capability and need to be addressed. In the present work, we initially designed and fabricated a vanadium nitride/carbon fiber (VN/CNF) composite via a facile electrospinning method followed by the ammonization process. The obtained VN/CNF composite anode exhibited excellent half/full sodium and potassium storage performance. When used as an anode material for SIBs, it delivered a high capacity of 403 mA h g at 0.1 A g after 100 cycles and as large as 237 mA h g at 2 A g even after 4000 cycles with negligible capacity fading. More importantly, the VN/CNFs//NaV(PO) full cell by coupling the VN/CNF composite anode with the NaV(PO) (NVP) cathode also exhibited a desirable capacity of 257 mA h g at 500 mA g after 50 cycles. Besides, when further evaluated as an anode for PIBs, the VN/CNF composite anode achieved a large capacity of 266 mA h g after 200 cycles at 0.1 A g and maintained a stable capacity of 152 mA h g at 1 A g even after 1000 cycles, showing significant long-term cycling stability. This is one of the best performances of vanadium-based anode materials for SIBs and PIBs reported so far.
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http://dx.doi.org/10.1039/c9nr10211fDOI Listing
May 2020

In situ fabrication of ultrathin few-layered WSe anchored on N, P dual-doped carbon by bioreactor for half/full sodium/potassium-ion batteries with ultralong cycling lifespan.

J Colloid Interface Sci 2020 Aug 13;574:217-228. Epub 2020 Apr 13.

Engineering Research Center of Polymer Green Recycling of Ministry of Education, College of Environmental Science and Engineering, Fujian Normal University, Fuzhou, Fujian 350007, China; Fujian Key Laboratory of Pollution Control & Resource Reuse, Fuzhou, Fujian 350007, China; Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), College of Chemistry, Nankai University, Tianjin 300071, China. Electronic address:

Sodium/potassium-ion batteries (SIBs/PIBs) with high electrochemical performance are promising but there still remain daunting challenges to explore an anode material with appealing cycling stability and rate capability. In addition, the utilization of waste biomass arouses tremendous researches in energy storage applications. Herein, we elaborately coupling ultrathin few-layered WSe nanosheets with N, P-doped biochar by utilizing waste chlorella as adsorbent and reactor. It displays a prominent long-term cycling property (265 mAh g at 1 A g up to 1500 cycles) in SIBs, which is the best long-cycle performance ever reported for WSe. Paired with NaV(PO) cathode, full SIBs also exhibit superior capacity of 210 mAh g at 0.5 A g for 120 cycles. Notably, we also report WSe-based anode material in PIBs, which delivers a high capacity of 333 mAh g at 0.1 A g for 100 cycles and superior cycling lifespan (155 mAh g at 1 A g up to 5300 cycles) as well as excellent rate properties. Additionally, the mechanism of the repeated process of sodiation/desodiation is revealed, by the deep characterization, such as ex-situ XRD/Raman, galvanostatic intermittent titration technique and CV measurements.
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http://dx.doi.org/10.1016/j.jcis.2020.04.055DOI Listing
August 2020

Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE-/- Mice.

Front Pharmacol 2020 13;11:223. Epub 2020 Mar 13.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Atherosclerosis and its associated cardiovascular diseases (CVDs) are serious threats to human health and have been reported to be associated with the gut microbiota. Recently, the role of berberine (BBR) in atherosclerosis and gut microbiota has begun to be appreciated. The purposes of this study were to observe the effects of high or low doses of BBR on atherosclerosis and gut microbiota modulation, and to explore their correlation in ApoE mice fed a high-fat diet. A significant decrease in atherosclerotic lesions was observed after treatment with BBR, with the effect of the high dose being more obvious. Both BBR treatments significantly reduced total cholesterol, APOB100, and very low-density lipoprotein cholesterol levels but levels of high/low-density lipoprotein cholesterol and lipoprotein (a) were only reduced by high-dose BBR. Decreased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6 and increased anti-inflammatory IL-10 and adiponectin levels were observed in the high-dose BBR group, but no decrease in IL-6 or increase in IL-10 was evident using the low-dose of BBR. 16S rRNA sequencing showed that BBR significantly altered the community compositional structure of gut microbiota. Specifically, BBR enriched the abundance of , , , , and , and changed the abundance of . These microbiota displayed good anti-inflammatory effects related to the production of short-chain fatty acids (SCFAs) and were related to glucolipid metabolism. and were significantly enriched in high-dose BBR group while and were more enriched in low-dose, and was enriched in both BBR doses. Metagenomic analysis further showed an elevated potential for lipid and glycan metabolism and synthesis of SCFAs, as well as reduced potential of TMAO production after BBR treatment. The findings demonstrate that both high and low-dose BBR can improve serum lipid and systemic inflammation levels, and alleviate atherosclerosis induced by high-fat diet in ApoE mice. The effects are more pronounced for the high dose. This anti-atherosclerotic effect of BBR may be partly attributed to changes in composition and functions of gut microbiota which may be associated with anti-inflammatory and metabolism of glucose and lipid. Notably, gut microbiota alterations showed different sensitivity to BBR dose.
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http://dx.doi.org/10.3389/fphar.2020.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083141PMC
March 2020

Enhanced cardiomyocyte reactive oxygen species signaling promotes ibrutinib-induced atrial fibrillation.

Redox Biol 2020 02 20;30:101432. Epub 2020 Jan 20.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. Electronic address:

Atrial fibrillation (AF) occurs in up to 11% of cancer patients treated with ibrutinib. The pathophysiology of ibrutinib promoted AF is complicated, as there are multiple interactions involved; the detailed molecular mechanisms underlying this are still unclear. Here, we aimed to determine the electrophysiological and molecular mechanisms of burst-pacing-induced AF in ibrutinib-treated mice. The results indicated differentially expressed proteins in ibrutinib-treated mice, identified through proteomic analysis, were found to play a role in oxidative stress-related pathways. Finally, treatment with an inhibitor of NADPH oxidase (NOX) prevented and reversed AF development in ibrutinib-treated mice. It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-β protein expression. It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins. Ibrutinib-treated mice were also more likely to develop AF, and AF occurred over longer periods. In conclusion, our study has established a pathophysiological role for ROS signaling in atrial cardiomyocytes, and it may be that ox-CaMKII and p-CaMKII (Thr-286) are activated by ROS to increase AF susceptibility following ibrutinib treatment. We have also identified the inhibition of NOX as a potential novel AF therapy approach.
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http://dx.doi.org/10.1016/j.redox.2020.101432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994714PMC
February 2020

A Pooled Analysis of the Prognostic Significance of Brugada Syndrome with Atrial Fibrillation.

Curr Pharm Des 2020 ;26(1):129-137

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF.

Methods: We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events.

Results: BrS patients with AF in all studies (OR 1.92, 95% CI:0.91to 4.04, P =0.09; Heterogeneity: P = 0.03, I2=61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P=0.91; Heterogeneity: P = 0.006, I2=80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P=0.002; Heterogeneity: P = 0.40, I2=0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001).

Conclusion: On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.
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http://dx.doi.org/10.2174/1381612826666200114112029DOI Listing
November 2020

Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target.

Front Pharmacol 2019 19;10:1360. Epub 2019 Nov 19.

Guang'an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Cardiovascular disease (CVD) is the leading cause of death worldwide, especially in developed countries, and atherosclerosis (AS) is the common pathological basis of many cardiovascular diseases (CVDs) such as coronary heart disease (CHD). The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide (TMAO), an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metabolism, and atherothrombosis. We also summarize available clinical studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events (MACE), in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.
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http://dx.doi.org/10.3389/fphar.2019.01360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877687PMC
November 2019

Role of cardioprotective agents on chemotherapy-induced heart failure: A systematic review and network meta-analysis of randomized controlled trials.

Pharmacol Res 2020 01 29;151:104577. Epub 2019 Nov 29.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Background: Although previous clinical randomized controlled trials (RCTs) have tested the effect of a variety of cardioprotective agents on cancer therapy-induced cardiotoxicity, the number of included patients was limited, and the results remained controversial. In this study, we aimed to evaluate the preventive or therapeutic effects of cardioprotective agents on heart failure (HF) caused by cardiotoxicity induced by cancer therapy.

Methods: We included trials of the following cardioprotective drugs: Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists and stains. We extracted the relevant information with predefined data extraction forms, and assessed the risk of bias in randomized controlled trials with the Cochrane risk of bias tool. The primary outcome was the left ventricular ejection fraction of patients after chemotherapy. We used the random-effects model to carry out pair-wise meta-analysis, and then carry out the random-effects network meta-analysis within the Bayesian framework.

Results: Twenty-two relevant RCTs, including 1 916 patients (79.6 % women) with a mean age of 48.4 years, were included. Based on the evaluation of all drug species from 20 studies (26 comparisons), the analysis found that 4 therapies, aldosterone antagonists (MD, 12.78 [95 % CI, 2.87-22.69] and MD, 13.75 [95 % CI, 2.21-25.30]), ACEIs (MD, 6.79 [95 % CI, 2.11-11.48] and MD, 7.76 [95 % CI, 2.64-12.88]), statin (MD, 8.35 [95 % CI, 1.11-15.59]), and beta-blockers (MD, 4.00 [95 % CI, 0.87-7.14]), had a higher efficacy than placebo and/or control, suggesting an LVEF protective effect of cardioprotective therapy. In the analysis classified by single drug or drug combination, based on 22 studies (31 comparisons), spironolactone (MD, 12.77 [95 % CI, 1.76-23.79] and MD, 14.62 [95 % CI, 1.70-27.55]), a combination of candesartan and carvedilol (MD, 12.40 [95 % CI, 0.99-23.81]), enalapril (MD, 7.35 [95 % CI, 1.16-13.54] and MD, 9.20 [95 % CI, 2.61-15.79]), and statin (MD, 8.36 [95 % CI, 0.36-16.36]) showed significant benefits in protecting left ventricular (LV) systolic function compared with the placebo and/or control.

Conclusion: When classified according to drug type, aldosterone antagonists, ACEIs, statins, and beta-blockers could substantially improve the LV systolic function. In the analysis classified by single drug or drug combination, spironolactone, enalapril, and statin have a significant cardioprotective effect. However, ARBs have no cardioprotective effect and fail to improve the LVEF.
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http://dx.doi.org/10.1016/j.phrs.2019.104577DOI Listing
January 2020

Does heart failure increase the risk of incident cancer? A meta-analysis and systematic review.

Heart Fail Rev 2020 11;25(6):949-955

Guang'an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Recently, several studies have demonstrated that heart failure (HF) may increase the risk of incident cancer. However, this association has not been statistically and systematically verified by any comprehensive pooled analyses. We performed a meta-analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer. From inception to April 2019, we searched PubMed and EMBASE for published relevant articles on patients with HF diagnosed with cancer afterwards, with reported outcomes of morbidity and mortality. Two investigators independently reviewed these included studies. Study data were independently extracted using predefined data extraction forms. Random and fixed-effects models were fit for the study duration. This analysis consisted of 4 cohort studies comprising 5,004,251 participants. The relative risk (RR) for incident cancer was 1.22 (95% confidence interval (CI), 1.13-1.33) indicating that patients with HF may have a higher risk of developing cancer. The pooled RR of co-mortality was 2.03 (95% CI, 1.13-3.65), indicating that HF associated with cancer increases the risk of mortality. In this meta-analysis and systematic review, our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality.
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http://dx.doi.org/10.1007/s10741-019-09876-0DOI Listing
November 2020

Combination of Counter Current Salting-Out Homogenous Liquid-Liquid Extraction with Dispersive Liquid-Liquid Microextraction for the High-Performance Liquid Chromatographic Determination of Environmental Estrogens in Water Samples.

J Chromatogr Sci 2020 Jan;58(2):171-177

College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province, 180 Wusi East Road, Lianchi District, Baoding, Hebei Province, 071002, China.

In this paper, counter current salting-out homogenous liquid-liquid extraction was combined with dispersive liquid-liquid microextraction for the determination of environmental estrogens in water samples by high-performance liquid chromatography. In this method, initially, sodium chloride was filled into a syringe and a mixture of water sample and acetonitrile was driven to pass through the syringe. Due to salting-out effect, fine droplets of acetonitrile went up through the remaining mixture and aggregated as a separated layer on the top. Then, the collected organic phase (acetonitrile) was removed with a syringe and mixed with carbon tetrachloride (extraction solvent). In the second step, the mixed organic phase was rapidly injected into 5 mL of distilled water to further enrich the analytes. Good linearity was obtained in the concentration range of 2.0~200 ng/mL for diethylstilbestrol (DES) and 8.0~200 ng/mL for octylphenol (OP), respectively. Limits of detection were 0.09 ng/mL for DES and 0.20 ng/mL for OP, respectively. Relative standard deviations for intra- and inter-day precisions were less than 2.1 and 3.1%, respectively. Finally, the established method was successfully applied to determine DES and OP in river water, well water, bottled water and campus drinking water samples with recoveries in the range from 81.0 to 105.9%.
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http://dx.doi.org/10.1093/chromsci/bmz080DOI Listing
January 2020

Domain and Switching Control of the Bulk Photovoltaic Effect in Epitaxial BiFeO Thin Films.

Sci Rep 2019 Sep 27;9(1):13979. Epub 2019 Sep 27.

Zentrum für Innovationskompetenz SiLi-nano, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), 06120, Germany.

Absence of inversion symmetry is the underlying origin of ferroelectricity, piezoelectricity, and the bulk photovoltaic (BPV) effect, as a result of which they are inextricably linked. However, till now, only the piezoelectric effects (inverse) have been commonly utilized for probing ferroelectric characteristics such as domain arrangements and resultant polarization orientation. The bulk photovoltaic effect, despite sharing same relation with the symmetry as piezoelectricity, has been mostly perceived as an outcome of ferroelectricity and not as a possible analytical method. In this work, we investigate the development of BPV characteristics, i.e. amplitude and angular dependency of short-circuit current, as the ferroelastic domain arrangement is varied by applying electric fields in planar devices of BiFeO films. A rather sensitive co-dependency was observed from measurements on sample with ordered and disordered domain arrangements. Analysis of the photovoltaic response manifested in a mathematical model to estimate the proportion of switched and un-switched regions. The results unravel the potential utility of BPV effect to trace the orientation of the polarization vectors (direction and amplitude) in areas much larger than that can be accommodated in probe-based techniques.
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http://dx.doi.org/10.1038/s41598-019-50185-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765050PMC
September 2019

Facile Synthesis of Ultra-Small Few-Layer Nanostructured MoSe Embedded on N, P Co-Doped Bio-Carbon for High-Performance Half/Full Sodium-Ion and Potassium-Ion Batteries.

Chemistry 2019 Oct 17;25(58):13411-13421. Epub 2019 Sep 17.

Engineering Research Center of Polymer Green Recycling of Ministry, of Education, College of Environmental Science and Engineering, Fujian Normal University, Fuzhou, Fujian, 35007, P. R. China.

Sodium/potassium-ion batteries (SIBs/PIBs) arouse intensive interest on account of the natural abundance of sodium/potassium resources, the competitive cost and appropriate redox potential. Nevertheless, the huge challenge for SIBs/PIBs lies in the scarcity of an anode material with high capacity and stable structure, which are capable of accommodating large-size ions during cycling. Furthermore, using sustainable natural biomass to fabricate electrodes for energy storage applications is a hot topic. Herein, an ultra-small few-layer nanostructured MoSe embedded on N, P co-doped bio-carbon is reported, which is synthesized by using chlorella as the adsorbent and precursor. As a consequence, the MoSe /NP-C-2 composite represents exceedingly impressive electrochemical performance for both sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). It displays a promising reversible capacity (523 mAh g at 100 mA g after 100 cycles) and impressive long-term cycling performance (192 mAh g at 5 A g even after 1000 cycles) in SIBs, which are some of the best properties of MoSe -based anode materials for SIBs to date. To further probe the great potential applications, full SIBs pairing the MoSe /NP-C-2 composite anode with a Na V (PO ) cathode also exhibits a satisfactory capacity of 215 mAh g at 500 mA g after 100 cycles. Moreover, it also delivers a decent reversible capacity of 131 mAh g at 1 A g even after 250 cycles for PIBs.
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http://dx.doi.org/10.1002/chem.201902899DOI Listing
October 2019

Regulatory Mechanisms of the NLRP3 Inflammasome, a Novel Immune-Inflammatory Marker in Cardiovascular Diseases.

Front Immunol 2019 10;10:1592. Epub 2019 Jul 10.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As a macromolecular complex, the NLRP3 inflammasome is activated to produce downstream factors, including caspase-1, IL-1β, and IL-18, which then promote local inflammatory responses and induce pyroptosis, leading to unfavorable effects. A growing number of studies have examined the relationship between the NLRP3 inflammasome and cardiovascular diseases (CVDs). However, some studies have shown that the NLRP3 inflammasome is not involved in the occurrence of certain diseases. Therefore, identifying the mechanism of action of the NLRP3 inflammasome and its potential involvement in the pathological process of disease progression is of utmost importance. This review discusses the mechanisms of NLRP3 inflammasome activation and the relationship between the inflammasome and CVDs, including coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies, and arrhythmia, as well as CVD-related treatments.
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http://dx.doi.org/10.3389/fimmu.2019.01592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635885PMC
June 2020

Pik3ip1 Is a Negative Immune Regulator that Inhibits Antitumor T-Cell Immunity.

Clin Cancer Res 2019 10 26;25(20):6180-6194. Epub 2019 Jul 26.

Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Stomatological Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.

Purpose: Multiple negative regulators restrict the ability of T cells to attack tumors. This work demonstrates the role of PI3K-interacting protein 1 (Pik3ip1) in restraining T-cell responses and antitumor immunity.

Experimental Design: An anti-Pik3ip1 mAb was generated to identify the Pik3ip1 expression pattern of hematopoietic cells. mice and a Pik3ip1 fusion protein were generated to investigate the effect of Pik3ip1 on T-cell-mediated antitumor immunity in MC38 and B16-F10 tumor models. Immunoblotting and confocal microscopy were used to identify inhibitory effects of Pik3ip1 on T-cell receptor (TCR) signaling. Pik3ip1 expression was quantified, and its impact on T-cell function in human tumors was measured.

Results: We demonstrated that Pik3ip1 was predominantly expressed on T cells and served as an essential rheostat for T-cell-mediated immunity. A Pik3ip1 genetic deficiency led to enhanced T-cell responsiveness upon immunization with a neoantigen. mice exhibited a marked increase in antitumor immunity and were resistant to tumor growth. Furthermore, Pik3ip1 extracellular domain fusion protein enhanced MC38 tumor growth was observed. Mechanistically, we found that Pik3ip1 inhibited TCR signaling by mediating the degradation of SLP76 through Pik3ip1 oligomerization via its extracellular region. Consistent with the results from the mouse models, PIK3IP1 expression correlated with T-cell dysfunction in human tumors.

Conclusions: Our data reveal a critical role for Pik3ip1 as a novel inhibitory immune regulator of T-cell responses and provide a potential molecular target for cancer immunotherapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-4134DOI Listing
October 2019

Meta-Analysis of Risk Stratification of SCN5A With Brugada Syndrome: Is SCN5A Always a Marker of Low Risk?

Front Physiol 2019 19;10:103. Epub 2019 Feb 19.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

with Brugada syndrome (BrS) is not commonly considered as an independent risk marker for subsequent cardiac events. However, the risk of combined with other clinical characteristics has not been fully investigated. The aim of this study is to investigate and evaluate risk stratification and related risk factors of in BrS. The databases of PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data were searched for related studies published from January 2002 to May 2018 followed by meta-analysis. The BrS patients who underwent gene tests were included. The prognosis and risk stratification of combined with symptoms and asymptoms diagnosis in BrS, electrophysiology study (EPS) were then investigated and evaluated. Outcomes were defined as ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD). Eleven suitable studies involving 1892 BrS patients who underwent gene tests were identified. (+) was not considered to be a significant predictor of future cardiac events (95% CI: 0.89-2.11; = 0.15; = 0%). However, (+) patients with symptoms at diagnosis revealed a higher prevalence of future VT/VF, SCD compared to (-) patients with symptoms at diagnosis. (95% CI: 1.06-3.70; = 0.03 = 0%) Among asymptomatic patients, the risk did not significantly differ between (+) patients and (-) patients. (95% CI: 0.51-4.72; = 0.45 = 0 %). In an investigation involving patients in EPS (-) BrS electrocardiogram (ECG), the risk of (+) is higher than that of (-) ( < 0.001). In BrS patients with symptoms at diagnosis or EPS (-), the meta-analysis suggests that (+) are at a higher risk of arrhythmic events than (-).
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http://dx.doi.org/10.3389/fphys.2019.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389868PMC
February 2019

Pooled Analysis of Risk Stratification of Spontaneous Type 1 Brugada ECG: Focus on the Influence of Gender and EPS.

Front Physiol 2018 31;9:1951. Epub 2019 Jan 31.

Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.

Risk stratification of patients with Brugada syndrome (BrS) is vital for accurate prognosis and therapeutic decisions. Spontaneous Type 1 ST segment elevation is generally considered to be an independent risk factor for arrhythmic events. Other risk factors include gender, syncope, sudden cardiac arrest (SCA), and positive electrophysiological study (EPS). However, the further risk stratification of spontaneous type 1 combined with the other risk factors remains unclear. The present study pooled data from 4 large trials aiming to systematically evaluate the risk of spontaneous Type-1 ECG when combined with one or more of these other recognized risk factors. We searched for related studies published from November 2, 2002 to February 10, 2018 in PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Databases. The pooled data were evaluated combining each risk factor with the presence of a spontaneous Type-1 ECG. All analyses were performed using Review Manager, version 5.0.12. Four eligible studies involving 1,338 patients (85% males, mean age: 48.1 ± 18.1 years) were enrolled. Spontaneous Type-1 ECG was associated with higher risk for ventricular tachycardia/fibrillation (VT/VF) than cases with non-Type 1 ECG in males (odds ratio: 95% CI: 1.84-5.17; < 0.0001), but not in females ( = 0.29). Among spontaneous Type-1 cases with syncope or with positive EPS, the difference was not statistically significant ( = 0.06 and 0.07, respectively). Patients with Type-1 ECGs and positive EPS were at higher risk than those with negative EPS (95% CI: 1.10-5.04; = 0.03). Pooled analysis showed an association of Spontaneous Type-1 ECG, Type-1 ECGs combined with male, and Type-1 ECGs combined with positive EPS between increased risk of arrhythmic events. Our results indicate that in BrS patients, a spontaneous Type-1 ECG is an independent risk factor for SCD in males, but not in females. A spontaneous Type-1 BrS is associated with a worse prognosis when combined with positive EPS.
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http://dx.doi.org/10.3389/fphys.2018.01951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365464PMC
January 2019
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