Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Evaluation of left ventricular systolic function in type 2 diabetes mellitus patients with and without peripheral vascular disease

BACKGROUND Peripheral vascular disease(PVD)is a common complication of type 2 diabetes mellitus(T2DM).Patients with T2DM have twice the risk of PVD as nondiabetic patients.AIM To evaluate left ventricular(LV)systolic function by layer-specific global longitudinal strain(GLS)and peak strain dispersion(PSD)in T2DM patients with and without PVD.METHODS Sixty-five T2DM patients without PVD,57 T2DM patients with PVD and 63 normal controls were enrolled in the study.Layer-specific GLS[GLS of the epimyocardium(GLSepi),GLS of the middle myocardium(GLSmid)and GLS of the endocardium(GLSendo)]and PSD were calculated.Receiver operating characteristic(ROC)analysis was performed to calculate the sensitivity and specificity of LV systolic dysfunction in T2DM patients with PVD.We calculated Pearson’s correlation coefficients between biochemical data,echocardiographic characteristics,and layer-specific GLS and PSD.RESULTS There were significant differences in GLSepi,GLSmid and GLSendo between normal controls,T2DM patients without PVD and T2DM patients with PVD(P<0.001).Trend tests revealed a ranking of normal controls>T2DM patients without PVD>T2DM patients with PVD in the absolute value of GLS(P<0.001).PSD differed significantly between the three groups,and the trend ranking was as follows:normal controls<T2DM patients without PVD<T2DM patients with PVD(P<0.001).ROC analysis revealed that the combination of layer-specific GLS and PSD had high diagnostic efficiency for detecting LV systolic dysfunction in T2DM patients with PVD.Lowdensity lipoprotein cholesterol was positively correlated with GLSepi,GLSmid and PSD(P<0.05),while LV ejection fraction was negatively correlated with GLSepi,GLSmid and GLSendo in T2DM patients with PVD(P<0.01).CONCLUSION PVD may aggravate the deterioration of LV systolic dysfunction in T2DM patients.Layer-specific GLS and PSD can be used to detect LV systolic dysfunction accurately and conveniently in T2DM patients with or without PVD.

Complications of Ziv-Aflibercept in Choroidal and Retinal Vascular Diseases

Introduction: The modern ophthalmology trends are changing rapidly every day with the introduction of much newer studies and research. Numerous anti-vascular endothelial growth factors (VEGF) are utilized as the mainstay in the treatment of intraocular vascular pathologies. The rationale of this study is to add to the literature regarding the safety and efficacy profile of the ziv-aflibercept as there is insubstantial data in patients with intraocular vascular pathologies being treated with this injection with prime focus on the complications of the injection. Materials and Methods: A prospective observational study was conducted at Opthalmology Department, Lahore General Hospital, Lahore between 14 August 2018 and 23 December 2019. Patients with choroidal and retinal vascular diseases like diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO) who had no active infection of eye and had no history of myocardial infarction or cerebrovascular accident were added in this study. Results: Best-corrected visual acuity was significantly improved at 4, 8, and 12 weeks as compared to the baseline (p Conclusion: The use of ziv-aflibercept injection via intravitreal route under aseptic conditions for choroidal and retinal vascular diseases is effective as well as safe with mild and treatable ocular side effects.

Gemcitabine-induced peripheral vascular disease and prolonged response in a patient with metastatic pancreatic adenocarcinoma:A case report

BACKGROUND Gemcitabine is an antimetabolite used in the treatment of pancreatic cancer.One of the side effects of gemcitabine is vascular toxicity.Here,we report the case of a patient treated with gemcitabine who had peripheral vascular disease concomi-tant with a prolonged antitumor response.CASE SUMMARY A 75-year-old man was diagnosed with locally recurrent pancreatic cancer.Partial response was achieved after 9 mo of gemcitabine.At the same time,the patient reported peripheral vascular disease without necrosis.Chemotherapy was suspended,and after one month the Positron Emission Tomography(PET)scan showed locoregional tumor recurrence.Gemcitabine was resumed and partial response was obtained,but peripheral vascular disease occurred.CONCLUSION Our results suggest that the appearance of peripheral vascular disease may be related to a prolonged response to gemcitabine.

Deep Neural Network Based Cardio Vascular Disease Prediction Using Binarized Butterfly Optimization

In this digital era,Cardio Vascular Disease(CVD)has become the lead-ing cause of death which has led to the mortality of 17.9 million lives each year.Earlier Diagnosis of the people who are at higher risk of CVDs helps them to receive proper treatment and helps prevent deaths.It becomes inevitable to pro-pose a solution to predict the CVD with high accuracy.A system for predicting Cardio Vascular Disease using Deep Neural Network with Binarized Butterfly Optimization Algorithm(DNN–BBoA)is proposed.The BBoA is incorporated to select the best features.The optimal features are fed to the deep neural network classifier and it improves prediction accuracy and reduces the time complexity.The usage of a deep neural network further helps to improve the prediction accu-racy with minimal complexity.The proposed system is tested with two datasets namely the Heart disease dataset from UCI repository and CVD dataset from Kag-gle Repository.The proposed work is compared with different machine learning classifiers such as Support Vector Machine,Random Forest,and Decision Tree Classifier.The accuracy of the proposed DNN–BBoA is 99.35%for the heart dis-ease data set from UCI repository yielding an accuracy of 80.98%for Kaggle repository for cardiovascular disease dataset.

Multi-target mechanism of triphala in cardio-cerebral vascular diseases based on network pharmacology

OBJECTIVE Numerous references made clear that triphala is revered as a multiuse therapeutic and perhaps even panacea historically.Nevertheless,the protective mechanism of triphala on cardio-cerebral vascular diseases(CCVDs)remains not comprehensive understanding.Hence,a network pharmacology-based method was suggested in this study to address this problem.METHODS This study was based on network pharmacology and bioinformatics analysis.Information on compounds in herbal medicines of triphala formula was acquired from public databases.Oral bioavailability as well as drug-likeness were screened by using absorption,distribution,metabolism,and excretion(ADME)criteria.Then,components of triphala,candidate targets of each component and known therapeutic targets of CCVDs were collected.Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources.In addition,key targets and pathway enrichment were analyzed by STRING database and DAVID database.Moreover,we verified three of the key targets(PTGS2,MMP9 and IL-6)predicted by using Western blotting analysis.RESULTS Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening,and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs.And 10 compounds,which actually linked to more than three genes,are determined as crucial chemicals.Core genes in this network were IL-6,TNF,VEGFA,PTGS2,CXCL8,TP53,CCL2,IL-10,MMP9 and SERPINE1.And pathways in cancer,TNF signaling path⁃way,neuroactive ligand-receptor interaction,etc.related to CCVDs were identified.In vitro experiments,the results indi⁃cated that compared with the control group(no treatment),PTGS2,MMP9 and IL-6 were up-regulated by treatment of 10μg·L^-1 TNF-α,while pretreatment with 20-80 mg·L^-1 triphala could significantly inhibit the expression of PTGS2,MMP9 and IL-6.With increasing Triphala concentration,the expression of PTGS2,MMP9 and IL-6 decreased.CON⁃CLUSION Complex components and pharmacological mechanism of triphala,and obtained some potential therapeutic targets of CCVDs,which could provide theoretical basis for the research and development of new drugs for treating CCVDs.

Diagnostic challenges in non-cirrhotic portal hypertension-porto sinusoidal vascular disease

Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension,which differ from cirrhosis through histological alterations,hemodynamic characterization and,clinical outcome.Because of the similarities in clinical presentation and imaging signs,frequently these patients,and particularly those with porto-sinusoidal vascular disease(PSVD),are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis.The most challenging differentiation to be considered is between PSVD and cirrhosis and,although not pathognomonic,liver biopsy is still the standard of diagnosis.Although they still require extended validation before being broadly used,new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease,like transient elastography,contrast-enhanced ultrasound or metabolomic profiling,have shown promising results.Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction,especially now when it is known that 40%of patients suffering from PSVD develop portal vein thrombosis.In this particular case,once the portal vein thrombosis occurred,the diagnosis of PSVD is impossible according to the current guidelines.Moreover,so far,the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances.In this review we highlighted the diagnostic challenges regarding the PSVD,as well as the current techniques used in the evaluation of these patients.

Extracellular matrix synthesis in vascular disease:hypertension,and atherosclerosis

Extracellular matrix （ECM） within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavail- ability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dys- regulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellu- lar and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease.

Neutrophil-to-lymphocyte ratio in occlusive vascular diseases： the literature review of the past 10 years

BACKGROUND: This study aims to evaluate the results of studies investigating neutrophilto-lymphocyte ratio(NLR) and to identify the prognostic and diagnostic value of NLR in occlusive vascular diseases.METHODS: With the aim of identifying the studies related to NLR, a search was performed on http://www.ncbi.nlm.nih.gov/pubmed by using the key words "neutrophil lymphocyte ratio" between January 2005 and December 2014. All of the original articles were evaluated according to date of publications, countries, clinics and topics. Studies about occlusive vascular diseases were evaluated according to their qualifications, review methods and results. SPSS for Windows 16.0 was used in data analysis and data were expressed as mean, standard deviation and percentage.RESULTS: A total of 735 original research articles were investigated. The number of publications have shown a regular logarithmic increase over the years. Thirty-two percent of all publications were performed by clinics in Turkey and 56.4% were performed by general-oncological surgery and cardiology clinics. A total of 107 publications were identified to be about occlusive vascular diseases, 80.3% of these publications were found to be prognostic and 19.6% to be diagnostic, 82.2% of them were found to be planned as retrospective and 17.7% as prospective. In 95.3% of prognostic publications, there was a positive correlation between high NLR values at admission and poor prognosis. In 95.3% of diagnostic publications high NLR values at admission were identifi ed to be signifi cant diagnostically.CONCLUSION: Elevated neutrophil-to-lymphocyte ratio at admission, could be used as a diagnostic and/or prognostic parameter in occlusive vascular diseases.

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease(amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment.

Current Status of Traditional Chinese and Western Medicine Treatment of Diabetic Peripheral Vascular Disease

Diabetic peripheral vascular disease(PVD)is one of the common chronic complications of diabetes.The main clinical manifestations of PVD are numbness and coldness of the limbs,resting pain,intermittent claudication,and other symptoms.The combined treatment involving Chinese and Western medicine for PVD has various clinical methods and definite curative effects.It is worthy of in-depth clinical research and application.

The Relationships between Respiratory Disease, Cardio-cerebral Vascular Disease and Temperature Change

Respiratory disease and cardio-cerebral vascular disease frequently occur in Anyang City. In this paper, by comparing incidence num- bers of respiratory disease and cardio-cerebral vascular disease in Anyang People＇s Hospital during 2010 -2012 with seasonal change of local tem- perature,it is found that they have obvious relationship, which has very important significance for preventing respiratory disease and cardio-cerebral vascular disease in the future.

Li Yunjie, an Expert on Cardio-Cerebral Vascular Diseases

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A Study on the Correlation Between Cerebral Small Vascular Disease and Constitution Types of Traditional Chinese Medicine

Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.

The role of pericyte in ocular vascular diseases

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells.They are pivotal in regulating blood flow,enhancing vascular stability,and maintaining the integrity of the blood-retina barrier/blood-brain barrier.The pluripotency of pericytes allows them to differentiate into various cell types,highlighting their significance in vascular disease pathogenesis,as demonstrated by previous studies.This capability enables pericytes to be a potential biomarker for the diagnosis and a target for the treatment of vascular disorders.The retina,an essential part of the eyeball,is an extension of cerebral tissue with a transparent refractive medium.It offers a unique window for assessing systemic microvascular lesions.Routine fundus examination is necessary for patients with diabetes and hypertension.Manifestations,such as retinal artery tortuosity,dilation,stenosis,and abnormal arteriovenous anastomosis,serve as typical hallmarks of retinal vasculopathy.Therefore,studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

A new perspective on changes in vascular function due to hypoxia

This review discusses the functions of blood vessels such as coagulation,regulation,immunity,endocrinology,and nerve conduction from a new perspective and suggests that hypoxia plays a common role in the changes in vascular function in various cardiovascular and cerebrovascular diseases.Therefore,it is oxygen therapy regulation may be a particularly beneficial means by which to regulate vascular function due to its low risk of harm and ease of implementation.Further,the authors have identified a link between vascular function and diseases caused by endogenous hypoxia and analyzed it in depth.The potential effects of hypoxia regulation schemes such as hyperxia,hyperoxic-hypoxia alternations,hypoxia preconditioning,and intermittent hypoxia on vascular function are also discussed,and we present theoretical support for targeted vascular therapy.

Biological behaviour and role of endothelial progenitor cells in vascular diseases

Objective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007. The search term was ＂endothelial progenitor cells＂. Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used. Results Progenitor cells in bone marrow, peripheral blood and adventitia can differentiate into mature endothelial cells （ECs）. The progenitor cells, which express certain surface markers including AC133, CD34 and KDR, enable restoration of the microcirculation and ECs when injury or ischaemia occurs. Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development. Moreover, their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors. Impairment of the progenitor cells might limit the regenerative capacity, even lead to the development of atherosclerosis or other vascular diseases. Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases. However, many challenges remain in understanding differentiation of endothelial progenitor cells, their mobilization and revascularization.

STIM1 and Orai1:novel targets for vascular diseases?

The past five years have witnessed the discovery of the endoplasmic reticulum calcium(Ca2+) sensor STIM1 and the plasma membrane Ca2+channel Orai1 as the bona fide molecular components of the store-operated Ca2+ entry(SOCE) and the Ca2+ release-activated Ca2+current(I CRAC) .It has been known for two decades that SOCE and ICRAC are required for lymphocyte activation as evidenced by severe immunodeficient phenotypes in patients lacking ICRAC.In recent years however,studies have uncovered expression of STIM1 and Orai1 proteins in various tissues and described additional roles for these proteins in physiological functions and pathophysiological conditions.Here,we will summarize novel findings pertaining to the role of STIM1 and Orai1 in the vascular system and discuss their potential use as targets in the therapy of vascular disease.

A bioinformatics method for predicting long noncoding RNAs associated with vascular disease

Long noncoding RNAs(lncRNAs)play important roles in human diseases including vascular disease.Given the large number of lncRNAs,however,whether the majority of them are associated with vascular disease remains unknown.For this purpose,here we present a genomic location based bioinformatics method to predict the lncRNAs associated with vascular disease.We applied the presented method to globally screen the human lncRNAs potentially involved in vascular disease.As a result,we predicted 3043 putative vascular disease associated lncRNAs.To test the accuracy of the method,we selected 10 lncRNAs predicted to be implicated in proliferation and migration of vascular smooth muscle cells(VSMCs)for further experimental validation.The results confirmed that eight of the 10 lncRNAs(80%)are validated.This result suggests that the presented method has a reliable prediction performance.Finally,the presented bioinformatics method and the predicted vascular disease associated lncRNAs together may provide helps for not only better understanding of the roles of lncRNAs in vascular disease but also the identification of novel molecules for the diagnosis and therapy of vascular disease.

Small-Molecule Fluorophores for Near-Infrared IIb Imaging and ImageGuided Therapy of Vascular Diseases

Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged.Here,we report novel benzobis(1,2,5-thiadiazole)-based second near-infrared region(NIR-II)fluorophores HY1-HY4 with highly twisted structures(55°at the S_(0) state),extremely strong aggregation-induced emission(AIE)characteristics(I/I_(0)>13),and remarkably high fluorescence quantum yields(QYs)(up to 14.45%)in the NIR-II region(>1000 nm)and∼0.27%in the nearinfrared IIb window(NIR-IIb,>1500 nm)in aqueous solution.Using NIR-IIb AIE HY4 dots,high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis,and real-time feedback of the therapeutic efficacy of Chinese medicine Dengzhan Xixin injection(DXI)on ischemic stroke,were achieved for the first time.In addition,results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway.These attractive results provide a new perspective for designing ultrabright NIR-IIb probes for vascular-related phenomena,disease assessment,and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.