Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.

Is frailty associated with short-term outcomes for elderly patients with acute coronary syndrome？

Background Frailty is a new prognostic factor in cardiovascular medicine due to the aging and increasingly complex nature of elderly patients. It is useful and meaningful to prospectively analyze the manner in which frailty predicts short-term outcomes for elderly patients with acute coronary syndrome （ACS）. Methods Patients aged 〉 65 years, with diagnosis of ACS from cardiology department and geriatrics department were included from single-center. Clinical data including geriatrics syndromes were collected using Comprehensive Geriatrics Assessment. Frailty was defined according to the Clinical Frailty Scale and the impact of the co-morbidities on risk was quantified by the coronary artery disease （CAD）--specific index. Patients were followed up by clinical visit or telephone consultation and the median follow-up time is 120 days. Following-up items included all-cause mortality, unscheduled return visit, in-hospital and recurrent major adverse cardiovascular events. Multivariable regression survival analysis was performed using Cox regression. Results Of the 352 patients, 152 （43.18%） were considered frail according to the study instrument （5-7 on the scale）, and 93 （26.42%） were considered moderately or se- verely frail （6-7 on the scale）. Geriatrics syndromes including incontinence, fall history, visual impairment, hearing impairment, constipation, chronic pain, sleeping disorder, dental problems, anxiety or depression, and delirium were more frequently in frail patients than in non-frail patients （P = 0.000, 0.031, 0.009, 0.014, 0.000, 0.003, 0.022, 0.000, 0.074, and 0.432, respectively）. Adjusted for sex, age, severity of coro- nary artery diseases （left main coronary artery lesion or not） and co-morbidities （CAD specific index） by Cox survival analysis, frailty was found to be strongly and independently associated with risk for the primary composite outcomes： all-canse mortality [Hazard Ratio （HR） = 5.393; 95% CI： 1.477-19.692, P = 0.011] and unscheduled return visit （HR - 2.832; 95% CI： 1.140-7.037, P = 0.025）. Conclusions Comprehensive Geriatrics Assessment and Clinical Frail Scale were useful in evaluation of elderly patients with ACS. Frailty was strongly and independently associated with short-term outcomes for elderly patients with ACS.

Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in acute ST-segment elevation myocardial infarction： a multicenter random- ized clinical trial

Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction （STEMI） patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate （40%-70%） stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban （15 pg/kg） were enrolled and were randomly assigned （h 1） to stenting group （n = 201） and non-stenting group （n = 198）. In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention （PCI） with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI （thrombectomy）, but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events （MACCE）, a composite of cardiac death, non-fatal myocardial infarction （M1）, repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group （adjusted HR： 0.42, 95% Ch 0.19-0.89, P = 0.02）. The stenting group had lower non-fatal MI rate than non-stenting group, （1.5% vs. 5.5%, P = 0.03）. The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.

Chinese expert consensus on the non-invasive imaging examination pathways of stable coronary artery disease

1 Introduction Early detection and diagnosis of stable coronary artery disease （SCAD） is essential for proactive secondary prevention of myocardial infarction （MI）, control of disease progress, and reduction of mortality. Clinical decision-making in modem medicine is increasingly dependent on cardiovascular imaging techniques. 2012 ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease has been issued by American Heart Association （AHA）. European Society of Cardiology （ESC） has issued 2013 ESC guidelines on the management of stable coronary artery disease.

Assessment of Coronary Stents by 64-slice Computed Tomography: In-stent Lumen Visibility and Patency

Objective To assess lumen visibility of coronary stents by 64-slice computed tomography （CT） coronary angiography, and determine the value of 64-slice CT in non-invasive detecting of in-stent restenosis after coronary artery stent implantation. Methods Totally, 60 patients （54 males, aged 57.0±12.7 years） and /05 stents were investigated by 64-slice CT at a mean interval of 20.0±16.6 months after coronary stents implantation. Axial multi-planar reconstruction images of the stents and curved-planar reconstruction images through the median of the stents were reconstructed for evaluating stent image quality on a 5-point scale （1=excellent, 5=nonassessable）, and stent lumen diameter was detected. Conventional coronary angiography was performed in 18 patients, and 32 stents were evaluated. Results Image quality was good to excellent on average （score 1.71±0.76）. Stent image quality score was correlated to heart rate （r=0. 281, P〈0.01） and stent diameter （r=-0.480, P〈0.001）. All the stents were assessable in lumen visibility with an average visible lumen diameter percentage of 60.7%±13.6%. Visible lumen diameter percentage was correlated to heart rate （r=-0.193, P〈0.05）, stent diameter （r=0.403, P〈0.001）, and stent image quality score （r=-0.500, P〈0.001）. Visible lumen diameter percentage also varied depending on the stent type. In comparison with the conventional coronary angiography, 4 of 6 in-stent stenoses were correctly detected. The sensitivity and specificity for the detection of in-stent stenosis were 66.7% and 84.6%, respectively. Conclusions Using a 64-slice CT, the stent lumen is partly visible in most of the stents. And 64-slice CT may be useful in the assessment of stent patency.

CORONARY ANGIOGRAPHY WITH DUAL SOURCE COMPUTED TOMOGRAPHY:INITIAL EXPERIENCE

Objective To explore the scan technique and image quality of coronary angiography with dual source computed tomography(CT) without oral metoprolol preparation.Methods Plain and enhanced dual source CT coronary angiography without oral metoprolol preparation was prospectively performed in 600 patients.Calcium scoring with plain scan images as well as multi-planar reconstruction(MPR),maximum intensity projection(MIP),and volume rendering technique(VRT) reconstruction with enhanced scan images were performed in all cases.The scan technique and post-reconstruction experience was summarized.The image quality was classified as 1 to 4 points,and coronary segments classified according to the American Heart Association standards were evaluated.Results The average calcium score of the 600 cases was 213.6±298.7(0-3 216.5).The average heart rate of the enhanced scan was 82.1±16.2(47-139) bpm.The post-reconstruction methods with which coronary segments could be shown as best as possible consisted of single phase reconstruction method,two or more phases supplemented method,and electrocardiogram editing method.Altogether 8 457 coronary segments were evaluated,among which 97.2% were evaluated as point 1,1.7% point 2,0.5% point 3,and 0.6% point 4.The coronary segments in 261 cases were completely normal,while 360 segments were diagnosed with <50% stenosis and 625 segments with ≥50% stenosis.Conclusions Excellent coronary artery image can be obtained with dual source CT in patients with any heart rate without oral metoprolol preparation.Heart rate is not a major source of the artifact,coronary segments can be well shown with single or multiple-phase reconstruction method.

Wild type transthyretin amyloidosis,a reason not to be forgotten for heart failure of preserved ejection fraction in the elderly

Amyloidosis is a multisystem disease that is characterized by deposition of fibrils in extracellular tissue,which mainly involves the kidney,heart,and autonomic nervous system.Two types of amyloidosis typically infiltrate the heart,including immunoglobulin light-chain(AL)and amyloid transthyretin(ATTR).ATTR is further subdivided into wild-type ATTR and variant ATTR caused by point mutations in the TTR gene.[1]Wild-type ATTR is considered as not uncommon in older patients with heart failure.Recently,a comprehensive set of consensus recommendations for the suspicion and diagnosis of ATTR was published,with particular focus on the combined application of noninvasive methods.[2]We present here a case of wild-type TTR cardiac amyloidosis(ATTRwt-CA),which was diagnosed by noninvasive modalities,and provide an overview of the recommended diagnostic approach of CA.Furthermore,to the best of our knowledge,this is the first Chinese case of ATTRwt-CA reported to date.

Chinese medical students’interest in COVID-19 pandemic

BACKGROUND The outbreak of coronavirus disease 2019(COVID-19)happened in early December and it has affected China in more ways than one.The societal response to the pandemic restricted medical students to their homes.Although students cannot learn about COVID-19 through clinical practice,they can still pay attention to news of COVID-19 through various channels.Although,as suggested by previous studies,some medical students have already volunteered to serve during the COVID-19 pandemic,the overall willingness of Chinese medical students to volunteer for such has not been systematically examined.AIM To study Chinese medical students’interest in the relevant knowledge on COVID-19 and what roles they want to play in the pandemic.METHODS Medical students at Peking Union Medical College were surveyed via a webbased questionnaire to obtain data on the extent of interest in the relevant knowledge on COVID-19,attitude towards volunteerism in the pandemic,and career preference.Logistic regression modeling was used to investigate possible factors that could encourage volunteerism among this group in a pandemic.RESULTS A total of 552 medical students responded.Most medical students showed a huge interest in COVID-19.The extent of students’interest in COVID-19 varied among different student-classes(P<0.05).Senior students had higher scores than the other two classes.The number of people who were‘glad to volunteer’in COVID-19 represented 85.6%of the respondents.What these students expressed willingness to undertake involved direct,indirect,and administrative job activities.Logistic regression analysis identified two factors that negatively influenced volunteering in the pandemic:Student-class and hazards of the voluntary job.Factors that positively influenced volunteering were time to watch COVID-19 news,predictable impact on China,and moral responsibility.CONCLUSION More innovative methods can be explored to increase Chinese medical students’interest in reading about the relevant knowledge on COVID-19 and doing voluntary jobs during the pandemic.

Hyperthyroidism-associated coronary spasm:A case of non-ST segment elevation myocardial infarction with thyrotoxicosis

Hyperthyroidism is associated with many heart diseases.Thyrotoxic state has a relationship with coronary spasm.We present a case of a non-menopausal woman with hyperthyroidism who complained of chest pain.The diagnosis of coronary spasm was confirmed by coronary angiography(CAG).She is treated well with anti-thyrotoxicosis and anti-anginal medication.We recommend not use CAG as the first diagnostic choice among the patients with medication-uncontrolled hyperthyroidism and chest pain.

RETROSPECTIVE ANALYSIS OF MAGNETIC RESONANCE MYOCARDIAL DELAYED ENHANCEMENT

Objective To explore the imaging and related clinical characteristics of magnetic resonance （MR） delayed enhancement in patients with ischemic or nonischemic heart disease. Methods Thirty-two cases who underwent MR myocardial cine and delayed enhancement imaging from January 2004 to October 2006 were retrospectively analyzed. The cine sequence imaging included the four-chamber view and the left ventricular short axis view. The delayed enhancement imaging was taken 10 minutes after the infusion of gadolinium from the antecubital vein with a segmented inversion-recovery-prepared Tl-weighted fast gradient echo sequence. Patients underwent coronary computed tomography angiography （CTA） two weeks before or after the MR imaging examination. Combined with clinical history, the clinical and MR imaging characteristics of the patients who had delayed enhancement were analyzed. Results MR delayed enhancement could be found in 16 cases. Among them, 12 cases had ischemic heart disease. Their coronary CTA showed one to three vessel diseases. The delayed enhancement was transmural or subendocardium, and the area of delayed enhancement corresponded well with one or more coronary arteries which had severe stenosis or occlusion. Four cases had nonischemic heart diseases One case was dilated cardiomyopathy, with diffuse small midwall spots in delayed enhancemen and only 30% stenosis of the anterior descending coronary artery in coronary CTA. One case was hypertrophic cardiomyopathy, with delayed enhancement of strip- and patch-shaped at midwall of the hypertrophic myocardiurn. One case was restrictive cardiomyopathy, and the delayed enhancement was located in the area of subendocardium of both the right and left ventricles. Coronary CTA of these two cases were normal The other case was a mass of the lateral wall of the left ventricle, and the delayed enhancement with a clumpy shape was located in the lateral wall of the left ventricle. Conclusions MR myocardial delayed enhancement is not a specific sign of myocardial infarction of ischemic heart disease. Nonischemic heart diseases including all kinds of primary cardiomyopathy and some other diseases affecting myocardium can also cause delayed enhancement, but their characteristics are different. The differentiation of the etiology of the nonischemic heart disease with delayed enhancement relies upon the intimate connection with clinical history and the cine sequence MR images.

Subclinical hypothyroidism and the metabolic syndrome:A meta-analysis of cross-sectional studies

AIM： To determine the relationship between subclini-cal hypothyroidism （SCH） and the metabolic syndrome（MS）. METHODS： We performed a systematic search of da-tabases [MEDLINE （July 1950 to July 2012）, EMBASE（July 1966 to July 2012）] and the references of identi-fied studies. Completely published cross-sectional stud-ies of a general population involving SCH and the MSwere included. The pooled odds ratio and weightedmean difference （WMD） for the outcomes were calcu-lated using random-effects models.RESULTS： Six cross-sectional studies with 19546 partic-ipants were included. In total, 398 of 1324 participants（30.06%） in the SCH group had the MS compared with 4975 of 18222 participants （27.30%） in the euthyroid group [OR = 1.20; 95%CI： 1.05-1.36; P = 0.004; χ2 = 2.53 （P = 0.773）; I2 = 0%]. Further analysis of the components of the MS showed that SCH was associatedwith increased body mass index （WMD, 0.32 kg/m2; 95%CI： 0.04-0.61; P = 0.026）, systolic blood pressure （WMD, 2.62 mmHg; 95%CI： 1.35-3.89; P 〈 0.001） and triglyceride （WMD, 0.25 mmol/L; 95%CI： 0.23-0.28; P 〈 0.001）.CONCLUSION： Based on the cross-sectional data, SCH may be associated with an increased risk of the MS, which could be attributed to the increased risk of metabolic components.

“In front of patients,I will always be a pupil.”Dr.Xiaoqian Zhang:the founder of the modern Chinese gastroenterology

Dr.Xiaoqian Zhang(张教骞,Hsiao-Chien Chang)was an outstanding clinician,therapist and medical educator,a member of the Academic Divisions of the Chinese Academy of Sciences,he is considered to be the founder of the modern Chinese gastroenterology(PUMCH,1988).As a doctor,he made a systemic and deep research on human blood volume,gastric secretion function,peptic ulcer disease,gastric ulcer and gastric cancer,celiac tuberculosis,amoebic dysentery,ulcerative colitis and so on.He diagnosed and treated multiple intractable diseases.As an educator,he emphasized the training of clinical basic skills,urged students to grasp the utilization of science in study and work.He trained a large number of talents for Chinese medicine.

Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure

Objective:The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure.Moreover,the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.Data sources:This study was based on data obtained from PubMed up to March 31,2019.Articles were selected using the following search terms:“gut microbiota,”“heart failure,”“trimethylamine N-oxide (TMAO),”“short-chain fatty acid (SCFA),”“bile acid,”“uremic toxin,treatment,diet,probiotic,prebiotic,antibiotic,” and “fecal microbiota transplantation.”Results:Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status.Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways,including the trimethylamine/TMAO,SCFA,bile acid,and uremic toxin pathways.Meanwhile,modulation of the gut microbiota through diet,pre/probiotics,fecal transplantation,and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders.Specifically,a few studies have focused on the cardioprotective effects of probiotics on heart failure.Conclusions:The composition of the gut microbiota in people with heart failure is different from those with healthy status.A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure.Moreover,an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent.More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease

Background: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. Methods: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. Results: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04–11.81;P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027;standard error 0.012;P < 0.05). Conclusions: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Intestinal Microbiota Metabolism and Atherosclerosis

Objective： This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease （CVD） and to propose a novel CVD therapeutic target. Data Sources： This study was based on data obtained from PubMed and EMBASE up to Jtme 30, 2015. Articles were selected using the following search terms： ＂＇Intestinal microbiota＂, ＂trimethylamine N-oxide （TMAO）＂, ＂trimethylamine （TMA）＂, ＂cardiovascular＂, and ＂atherosclerosis＂. Study Selection： Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results： A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions： Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management.

Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study

Background and purpose Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease(CSVD),previous findings remain largely inconclusive and vary according to disease status and study designs.The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.Methods A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects.The biomarker panel was grouped as follows:systemic inflammation(high-sensitivity C reactive protein(hsCRP),interleukin 6 and tumour necrosis factorα),endothelial-related inflammation(E-selectin,P-selectin,intercellular adhesion molecule 1,vascular cell adhesion molecule 1(VCAM-1),CD40 ligand,lipoprotein-associated phospholipase A2,chitinase-3-like 1 protein and total homocysteine(tHCY))and media-related inflammation(matrix metalloproteinases 2,3 and 9,and osteopontin).The association(s)between different inflammatory groups and white matter hyperintensity(WMH),lacunes,cerebral microbleeds(CMBs),enlarged perivascular space(PVS)and the number of deep medullary veins(DMVs)were investigated.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=0.254,p=0.027).Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH(β=0.063,p=0.005)and tHCY was significant for lacunes(β=0.069,p<0.001).There was no association between any group of inflammatory biomarkers and CMBs or PVS.Systemic inflammatory biomarkers were associated with fewer DMVs(R^(2)=0.032,p=0.006),and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP(β=−0.162,p=0.007)was significant.Conclusion WMH and lacunes were associated with endothelial-related inflammatory biomarkers,and fewer DMVs were associated with systemic inflammation,thus suggesting different underlying inflammatory processes and mechanisms.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Immunotherapy for the rheumatoid arthritis-associated coronary artery disease: promise and future

Objective:To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis(RA)-associated coronary artery disease(CAD),and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen.Data sources:This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations,including coronary artery disease,myocardial ischemia,cardiovascular diseases,RA,rheumatic diseases,treatment,therapy,strategies,immunotherapy,inflammation,and anti-inflammation.Study selection:All retrieved literature was scrutinized,most relevant articles about the pathogenic mechanism and clinical management,especially anti-inflammatory therapy of RA-associated CAD were reviewed.Results:RA is an immune-mediated chronic inflammatory disease which has a great social disease burden.In addition to typical arthritic manifestations,RA also affects extra-articular tissues and organs,within which the involvement of the cardiovascular system,especially incorporating CAD,is the leading cause of death for patients with RA.Recently,numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA.The effect of traditional RA drugs on CAD risk management has been gradually clarified,and more emerging biologic agents are being explored and studied,which have also achieved satisfactory outcomes.Furthermore,with the success of the CANTOS clinical trial,novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect.Conclusions:RA is an independent risk factor for CAD,which mainly results from the underlying inflammatory cascade;therefore,anti-inflammatory therapy,especially the emerging novel biologic drugs,is important for CAD management in patients with RA and may also be a promising approach among the general population.

Metabolic syndrome, intracranial arterial stenosis and cerebral small vessel disease in community- dwelling populations

Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a community-based sample.Methods This study included 943 participants(aged 55.6±9.2 years,36.1%male)from the community-based Shunyi cohort study.MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score.ICAS was evaluated by brain magnetic resonance angiography.The MRI markers of CSVD,including white matter hyperintensities(WMHs),lacunes,cerebral microbleeds(CMBs)and enlarged perivascular spaces(EPVS),were assessed.Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.Results We found that risk of ICAS(OR=1.75,95%CI 1.39 to 2.21,p<0.001)increased consistently with MetS severity.MetS severity was significantly associated with higher risks of WMH volume(β=0.11,95%CI 0.01 to 0.20,p=0.02)and lacunes(OR=1.28,95%CI 1.03 to 1.59,p=0.03)but not the presence of CMBs(OR=0.93,95%CI 0.74 to 1.16,p=0.51)and PVS severity(EPVS in basal ganglia:OR=0.96,95%CI 0.84 to 1.09,p=0.51 and EPVS in white matter:OR=1.09,95%CI 0.96 to 1.23,p=0.21).Conclusions Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery,whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

Relationship between Neutrophil-to-Lymphocyte Ratio and Pulse Wave Velocity in Young Patients with Systemic Lupus Erythematosus

Background： The incidence of atherosclerosis-related myocardial infarction can be as much as 50-fold greater in young patients with systemic lupus e~,thematosus （SLE） than in age-matched controls. There are several explanations for this phenomenon, all of which result in a chronic state of low-grade inflammation. Recently, the neutrophil-to-lynlphocyte ratio （NLR） has been proposed as a useliil biomarker of inflammation. Pulse wave velocity （PWV） is a reliable indicator of vascular damage and atherosclerosis. There is a paucity of data concerning the relationship between NLR and atherosclerosis as measured by PWV in patients with SLE. This study aimed to verify whether there is a positive correlation between NLR and PWV and to explore factors that influence PWV in young SLE patients. Methods： A total of 90 female patients with SLE were enrolled in this cross-sectional investigation. Traditional and nontraditional cardiovascular risk factors were assessed on the same day that brachial-ankle PWV （baPWV） was examined. The patients were divided into three groups according to their mean baPWV values： patients whose mean baPWV value was lower than the first tertile were placed in Group 1 ： patients whose mean baPWV value was between the first tertile and the second tertile were placed in Group 2： and patients whose mean baPWV value was higher than the second tertile were placed in Group 3. SPSS 20.0 was used to perform all statistical analyses in this study. Both univariate linear regression and multivariate regression models were utilized to analyze the association between NLR and arterial stiffness. Results： Systolic blood pressure, diastolic blood presstire （DBP）. and triglycerides were all significantly different among Groups 1,2, and 3 （ 111.90 ± 12.85 mmHg vs. 114.60 ± 12.88 mmHg vs. 129.43 ±16.21 mmHg, P 〈 0.001 ： 68.77 ± 8.63 mmHg vs. 71.87 ± 9.77 mmHg vs. 82.57 ± 14.89 mmHg, P 〈 0.001 ; and 1.44 [0.91-2.47] mmol/L vs. 0.98 [0.78-1.26] mmol/L vs. 2.20 [0.94-3.66] mmol/L P = 0.030： respectively）, as were creatinine （57.50 [52.00-69.00] mmol/L vs. 55.50 [49.00-64.00] mmol/L vs. 64.00 [56.00-86.00] mmol/L P = 0.045） and blood urea nitrogen （4.27 [3.79-6.22] mmol/L vs. 4.16 [3.47-4.84] mmol/L vs. 5.88 [4.04-8.19] mmol/L, P = 0.011 ）. NLRs were significantly different among Groups 1, 2, and 3 （2.16 [1.56-3.42] vs. 3.12 [1.91-4.19] vs. 5.29 [2.63-7.25], P = 0.001）. N LR, together with DBP and the SLE disease activity index, independently predicts PWV. Conclusions： This study demonstrated that there was a positive correlation between NLR and PWV. Moreover, we found that disease activity and DBP were also positively correlated with PWV.