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.

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.

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.

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.

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.

Mirror writing in elderly patients with Alzheimer disease and vascular dementia

BACKGROUND： The results showed that mirror writing （MW） was correlated with the development of written language, so that MW examination may be one of methods to examine the intelligence of elderly people. OBJECTIVE： To study the MW in elderly patients with Alzheimer disease （AD） and vascular dementia （VaD） and take appropriate scale for their evaluation. DESIGN： Taking the written portion of the Chinese Aphasia Examination Scale （1994） for assessment. SETTING： Department of Neurology, Neuropsychological Laboratory, Beijing Hospital. PARTICIPANTS： From March 1998 to January 2001, 33 patients with AD, 30 patients with VaD admitted into Department of Neurology, Beijing Hospital was enrolled into study. Criteria according to the Diagnostic and Statistical Manual of Mental Disorder, 4^th edition （DSM-Ⅳ）, published by the American Psychiatric Association was used to diagnose AD, while criteria according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour 1a Recherche et 1＇ Enseignement en Neurosciences （NINDS-AIREN） and Alzheimer Disease Diagnostic and Treatment Center （ADDCT） were used for diagnosis of VaD. AD group contained 19 males and 14 females aged 60 - 83 years. Twenty-eight males and 2 females, aged 60 - 87 years made up the VaD group. The 63 healthy elderly subjects matched on age and education as controls were enrolled into study. The matched controls were categorized AD control （n =33） and VaD control （n =30）. All patients and controls were understanding and agree with all items of assessment. METHODS： MW examination, Mini Mental State Examination （MMSE）, Hachinski Ischemic Scale, the Global Deterioration Scale （GDS） were examined in all subjects. ① Use the written potion of the Chinese Aphasia examination Scale （1994）, patient using MW for 91% - 100% of dictation had complete MW, those using MW for 51% - 90% of dictation had severe MW, those using MW for 11% - 50% had moderate MW, those using MW for 1% - 10% had mild MW. ② According to the MMSE, the patients were considered to have dementia if they were illiterate and had an MMSE score ≤ 17 score or educated time ≤ 6 years and MMSE ≤ 20 score or educated time 〉 6 years and MMSE ≤ 24 score. ③Using the Hachinski Ischemic Scale to differentiate the AD and VaD, it included 6 items and total 9 scores. 〉 7 score was VaD, 〈 4 score was AD and 4 - 7 score was blended dementia. ④ Using the GDS to assess cognitive function： Standard criteria were divided in 7 degrees： 1 degree： no impairment of cognition and 7 degree： very severe impairment of cognition. MAIN OUTCOME MEASURES： The data of MW examination, evaluation of MMSE, Hachinski Ischemic Scale and the GDS of all assessed subjects. RESULTS： All 63 cases of AD and VaD and 63 healthy controls were entered for analysis. ①Results of MW examination： A total of 17 patients with AD were characterized as using MW, 3 with moderate MW and 14 patients with mild MW. In the corresponding control group, only 2 subjects were characterized as being mild MW. The VaD group has 23 patients with MW, 2 with moderate and 21 patients with mild MW. ② MMSE score： MMSE score of AD group was much lower than that of individuals in control group [（20.15 ± 3.40）, （29.73 ±0.40） score, P 〈 0.01 ], MMSE score of VaD group was much lower than that of individuals in control group [09.33±2.75）, （29.12±0.63） score, P 〈 0.01]. ③Hachinski Ischemic Scale and GDS score： Rating according to the Hachinski Ischemic Scale was higher in VaD patients compared to AD patients [（9.61 ±1.69）, （1.09±0.60） score, P 〈 0.01]. The GDS score did not significantly differ between the AD group and the VaD group. CONCLUSION： ① MW examination could be used as an indicator of intelligence in healthy elderly people and also could be used as one of methods to assess the intelligence in AD and VaD patients. ② Grade of severity of MW may indirectly reflect the degree of dementia.

Distribution of ApoE Gene Polymorphism and Significance of Auxiliary Diagnosis and Treatment of Cerebrovascular Diseases(Intracerebral Hemorrhage and Cerebral Thrombosis) in the Longyan Area

Objective:To make statistics on the distribution of ApoE gene polymorphism in the Longyan area,provide data for the statistics of regional cerebrovascular diseases,explore the significance of ApoE gene polymorphism distribution for clinical guidance,diagnosis and treatment,and provide more suggestions for clinical diagnosis and treatment of cerebrovascular diseases.Methods:800 patients with cerebrovascular disease in the Longyan area from July 2018 to April 2021 were selected as the research object,and 800 normal healthy patients were selected as the control group.The data were further analyzed according to the collected patient information,and the patients were distinguished according to age and other basic information,the type of cerebrovascular disease,ApoE gene polymorphism and blood lipid test results.The distribution of ApoE gene polymorphism in the cerebrovascular disease population in the Longyan area was given to determine the correlation between the incidence of cerebrovascular disease and the distribution of ApoE gene polymorphism.Results:In the study group,E2/E3 genotyping was the most common 400(50.00%),and E4/E4 genotyping 6(0.75%)was the least common;In the control group,E2/E4 genotyping was the most common 480(60.00%),and E2/E3 genotyping accounted for the second 290(36.25%).In the study group,E3 allele was the most common 383(47.88%),E4 allele 121(15.12%);in the control group,E2 allele was the most common391(48.88%),and E3 allele 142(17.75%).Conclusion:According to the statistics of ApoE gene polymorphism distribution in the Longyan area and the analysis of the correlation of other cerebrovascular diseases,it is found that E2/E3 genotype may be related to cerebrovascular diseases,and E3 allele may be a susceptibility factor.Through the above analysis,the occurrence of diseases can be predicted and prevented.

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.

Chloride channels in vascular function and disease

Vascular smooth muscle cells（VSMCs） are the major component of vascular wall which are often stretched and compressed by pounding intravascular pressure.These mechanical signals are usually transformed to electrical signals by the opening or closing of ion channels in VSNCs and endothelial cells.Intravascular pressure causes a graded membrane potential depolarization of the VSMCs and leads to vasoconstriction（i.e.,myogenic response）,independent of the vascular endothelium. Although the important role of cation channels including L-type Ca2+ channels,K+ channels,and TRP channels in the regulation of vascular tone has been well established the functional roles played by Cl- channels in the regulation of the membrane potential and vascular tone remain essentially obscure. Recent emerging evidence implicates very important roles of Cl- channels in vascular function ranging from the control of membrane potential equilibrium, vascular contraction and relaxation to the regulation of intracellular pH,cell volume homeostasis,cell proliferation,migration,and apoptosis.

Microbleeds in fronto-subcortical circuits are predictive of dementia conversion in patients with vascular cognitive impairment but no dementia

Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.