Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma:Retrospective study

BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network

BACKGROUND Hepatocellular carcinoma(HCC)recurrence is highly correlated with increased mortality.Microvascular invasion(MVI)is indicative of aggressive tumor biology in HCC.AIM To construct an artificial neural network(ANN)capable of accurately predicting MVI presence in HCC using magnetic resonance imaging.METHODS This study included 255 patients with HCC with tumors<3 cm.Radiologists annotated the tumors on the T1-weighted plain MR images.Subsequently,a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC.Postoperative pathological examination is considered the gold standard for determining MVI.Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm.RESULTS Using the bagging strategy to vote for 50 classifier classification results,a prediction model yielded an area under the curve(AUC)of 0.79.Moreover,correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI,whereas tumor sphericity was significantly correlated with MVI(P<0.01).CONCLUSION Analysis of variable correlations regarding MVI in tumors with diameters<3 cm should prioritize tumor sphericity.The ANN model demonstrated strong predictive MVI for patients with HCC(AUC=0.79).

Prevalence of Microvascular Complications and Associated Risk Factors among Diabetes Mellitus Patients Attending Nyeri County Referral Hospital, Kenya: A Cross-Sectional Study

Microvascular complications are one of the major causes of morbidity and mortality worldwide among patients with diabetes mellitus (DM). More than 50% of Nyeri County Referral Hospital (NCRH) admissions result from non-communicable diseases (NCDs) and over 55% of hospital deaths are attributable to NCDs. In Kenya, Nyeri County has the highest prevalence of diabetes mellitus compared to other counties. This study therefore sought to assess the prevalence of microvascular complications and the associated risk factors among patients attending Nyeri County Referral Hospital in Kenya. A hospital-based cross-sectional study was conducted on 314 DM patients on follow-up at NCRH from August 2022 to October 2022. Data were analyzed using STATA version 17. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with Microvascular complications of DM. Among the 314 participants with DM, 58% were females. The overall prevalence of Microvascular complications (MVCs) is 36.62%. Diabetic peripheral neuropathy was the most frequent complication (27.4%). Inadequate physical exercise was a risk factor for all MVCs. Age, marital status, and level of education were risk factors for neuropathy while smoking and alcohol intake were risk factors for nephropathy. Non-smokers were 98% less likely to have nephropathy (OR = 0.024;95% CI 0.003 - 0.145). The odds of those who exercise once weekly getting retinopathic complications reduced by 83% (OR = 0.18, 95% CI 0.049 - 0.398) compared to those who exercise daily. The findings highlight the implication of lifestyle factors in the development of MVCs among DM patients. Therefore, benefits of microvascular complications prevention should thus be factored into the management of patients with diabetes mellitus.

Development and Innovation of Modern Microvascular Anastomoses

High-quality microvascular anastomosis is the foundation of successful microsurgery and one of the most important basic skills for microsurgeons. The traditional manual suture is recognized as the “gold standard” for microvascular anastomosis, but it still has problems such as long operation time and easy to cause vascular damage. In order to improve the success rate of microvascular anastomosis, reduce surgical complications and make the prognosis of patients better. In order to improve the success rate of microvascular anastomosis and reduce the surgical complications, scholars at home and abroad have developed some new vascular anastomosis techniques that are simple, fast and minimally invasive while improving the traditional surgical suturing methods. In this paper, we review the microvascular anastomosis, and its application research in two methods of traditional hand suture and non-suture anastomosis, in order to promote the application development of microvascular anastomosis.

A historical literature review of coronary microvascular obstruction and intra-myocardial hemorrhage as functional/structural phenomena

The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused hearts subjected to ischemia/reperfusion(I/R)do not suggest the involvement of microembolization and microthrombi in this phenomenon.The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction.Consequently,the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi,platelets,and neutrophils.Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries.However,reperfusion triggers more pronounced damage,possibly mediated by pyroptosis.MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling.Therefore,pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles.Ischemic conditioning protocols have been shown to prevent MVO,with L-type Ca2+channel blockers appearing the most effective in treating MVO.

Postoperative adjuvant therapy for hepatocellular carcinoma with microvascular invasion

Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after curative treatment are still high and overall survival is unsatisfactory.Microvascular invasion(MVI)is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival.Unfortunately,whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown.In this review,we summarize the therapeutic effects of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,tyrosine protein kinase inhibitor-based targeted therapy,and immune checkpoint inhibitors in patients with MVI after LR or LT,aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.

Role of apigenin in high glucose-induced retinal microvascular endothelial cell dysfunction via regulating NOX4/p38 MAPK pathway in vitro

AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction

Objective To investigate the impact of microvascular obstruction(MVO)on the global and regional myocardial function by cardiac magnetic resonance feature-tracking(CMR-FT)in ST-segment-elevation myocardial infarction(STEMI)patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1-7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study.Based on the presence or absence of MVO on late gadolinium enhancement images,patients were divided into groups with MVO and without MVO.The infarct zone,adjacent zone,and remote zone were determined based on a myocardial 16-segment model.The radial strain(RS),circumferential strain(CS),and longitudinal strain(LS)of the global left ventricle(LV)and the infarct,adjacent,and remote zones were measured by CMRFT from cine images and compared between patients with and without MVO using independent-samples t-test.Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients(mean age 56.66±11.38 years)were enrolled.MVO was detected in 37.58%(59/157)of STEMI patients,and the mean size of MVO was 3.00±3.76 mL.Compared with patients without MVO(n=98),the MVO group had significantly reduced LV global RS(t=-4.30,P<0.001),global CS(t=4.99,P<0.001),and global LS(t=3.51,P=0.001).The RS and CS of the infarct zone in patients with MVO were significantly reduced(t=-3.38,P=0.001;t=2.64,P=0.01;respectively)and the infarct size was significantly larger(t=8.37,P<0.001)than that of patients without MVO.The presence of LV MVO[OR=4.10,95%CI:2.05-8.19,P<0.001]and its size[OR=1.38,95%CI:1.10-1.72,P=0.01],along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis,while only heart rate(OR=1.08,95%CI:1.03-1.13,P=0.001)and LV infarct size(OR=1.10,95%CI:1.03-1.16,P=0.003)were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO,and MVO deteriorates the global and regional LV myocardial function.

Preoperative prediction of microvascular invasion in hepatocellular carcinoma using ultrasound features including elasticity

BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy.Shear wave elastography(SWE)plays an important role in hepatic imaging,but its value in the preoperative prediction of MVI in HCC has not yet been proven.AIM To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC.METHODS Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study.Conventional ultrasound features and SWE features such as maximal elasticity(Emax)of HCCs and Emax of the periphery of HCCs were acquired before surgery.These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs.RESULTS This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs,including 54 with mild MVI and 48 with severe MVI.Maximal tumor diameters,surrounding liver tissue,color Doppler flow,Emax of HCCs,and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs.In addition,Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs.Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI,with odds ratios of 2.820 and 1.021,respectively.CONCLUSION HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI.Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.

Exploring the mechanism of icariin in regulat⁃ing cardiac microvascular endothelial cells based on network pharmacology,molecular docking and in vitro experiments

OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment to construct a myocardial ischemiareperfusion model,and were divided into normal,model,low(10μmol·L^(-1)),medium(20μmol·L^(-1))and high(40μmol·L^(-1))ICA group,and high ICA+inhibitor group(40μmol·L^(-1)+20 nmol·L^(-1)).CCK-8 assay was used to assess the protective ability of ICA against CMEC,and cell migration assay and tube-formation assay were used to detect the migration and generation ability of CMEC.The TCMSP database,Swiss-Target database and literature mining methods were used to col⁃lect ICA-related targets,the GeneCards data⁃base was used to collect target genes related to myocardial ischemia/reperfusion,and Cytoscape 3.8.0 software was used to construct a"drug-tar⁃get-disease"network.The potential targets were imported into STRING 11.5 database to obtain the PPI network.GO and KEGG enrichment analyses were performed on the potential targets using the DAVID database.Molecular docking was performed using AutoDock-vina 1.1.2 soft⁃ware.Western blot detected the expression of related proteins.RESULTS After CMEC was subjected to OGD/R treatment,ICA had a protec⁃tive effect at 10^(-1)60μmol·L^(-1);the results of the cell migration assay showed that each group of ICA could promote the migratory effect of CMEC(P<0.01,P<0.01);and the results of tube-for⁃mation assay showed that each group of ICA could significantly promote the generation of branches(P<0.01)and the capillary length exten⁃sion(P<0.05).Network pharmacology collected a total of 23 ICA action targets,1500 disease tar⁃gets and 12 key targets.GO function enrichment analysis found 85 results.KEGG pathway enrich⁃ment analysis found 53 results,involving AGERAGE signaling pathway,sphingolipid signaling pathway and VEGF signaling pathway.Molecu⁃lar docking results showed that ICA had better binding with core targets PRKCB,PRKCA and PTGS2.Western blot results showed that ICA could regulate the expression of PRKCB,PRKCA and PTGS2 proteins.The results of cell migra⁃tion assay,tube-formation assay and protein expression were reversed after addition of PKC inhibitor.CONCLUSION The potential mecha⁃nism of action of ICA against myocardial isch⁃emia-reperfusion injury may be related to the reg⁃ulation of processes such as CMEC migration and angiogenesis,and it functions through the key target gene PKC.

Down-regulation of histone deacetylase 7 reduces biological activities of retinal microvascular endothelial cells under high glucose condition and related mechanism

AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.

Diagnostic use of superb microvascular imaging in evaluating septic arthritis of the manubriosternal joint:A case report

BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic.Conventional ultrasound,plain radiographs,and computed tomography are not able to confirm or even suspect arthritis early.Superb microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular patterns.The higher sensitivity for increased perisynovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging(MRI).CASE SUMMARY A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right arm.Traumatic injury and the most common respiratory and cardiac disorders were ruled out.Blood cultures came back positive for Staphylococcus aureus,and sepsis was confirmed.A small lump was noted on the chest during the first week of hospitalization.Superb microvascular imaging was performed and septic arthritis of the manubriosternal joint was detected.MRI confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the sternum.The patient was treated for three weeks with intravenous antibiotics and the outcome was favorable:Inflammatory markers became normal,and the lump disappeared.Three months later,the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with MRI.CONCLUSION Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.

Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma

BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.

Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke

Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions.

Glucagon-like peptide-1 protects against cardiac microvascular endothelial cells injured by high glucose

Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.