In situ staining of the primo vascular system in the ventricles and subarachnoid space of the brain by trypan blue injection into the lateral ventricle

We examined a new method for visualization of the primo vascular system in the rat brain involving lateral ventricle injection of trypan blue. Results showed that the primo vascular system in the lateral ventricles and arachnoid mater of the brain were preferentially stained relative to blood vessels and fascia. The primo-vessels along blood vessels in the brain were clearly exhibited. In addition, the primo vascular system was evident between the fourth ventricle and the quadrigeminal cistern. Our experimental findings indicate that this new technique of lateral ventricle injection of trypan blue can visualize the primo vascular system in lateral ventricles and arachnoid mater of rats in situ.

Microfluidic chips for the endothelial biomechanics and mechanobiology of the vascular system

Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.

Effects of ketogenic diet and ketone bodies on the cardiovascular system:Concentration matters

Ketone bodies have emerged as central mediators of metabolic health,and multiple beneficial effects of a ketogenic diet,impacting metabolism,neuronal pathologies and,to a certain extent,tumorigenesis,have been reported both in animal models and clinical research.Ketone bodies,endogenously produced by the liver,act pleiotropically as metabolic intermediates,signaling molecules,and epigenetic modifiers.The endothelium and the vascular system are central regulators of the organism’s metabolic state and become dysfunctional in cardiovascular disease,atherosclerosis,and diabetic micro-and macrovascular complications.As physiological circulating ketone bodies can attain millimolar concentrations,the endothelium is the first-line cell lineage exposed to them.While in diabetic ketoacidosis high ketone body concentrations are detrimental to the vasculature,recent research revealed that ketone bodies in the low millimolar range may exert beneficial effects on endothelial cell(EC)functioning by modulating the EC inflammatory status,senescence,and metabolism.Here,we review the long-held evidence of detrimental cardiovascular effects of ketoacidosis as well as the more recent evidence for a positive impact of ketone bodies—at lower concentrations—on the ECs metabolism and vascular physiology and the subjacent cellular and molecular mechanisms.We also explore arising controversies in the field and discuss the importance of ketone body concentrations in relation to their effects.At low concentration,endogenously produced ketone bodies upon uptake of a ketogenic diet or supplemented ketone bodies(or their precursors)may prove beneficial to ameliorate endothelial function and,consequently,pathologies in which endothelial damage occurs.

Radiological features of uncommon aneurysms of the cardiovascular system

Although aortic aneurysms are the most common type encountered clinically, they do not span the entire spectrum of possible aneurysms of the cardiovascular system. As cross sectional imaging techniques with cardiac computed tomography and cardiac magnetic resonance imaging continue to improve and becomes more commonplace, once rare cardiovascular aneurysms are being encountered at higher rates. In this review, a series of uncommon, yet clinically important, cardiovascular aneurysms will be presented with review of epidemiology, clinical presentation and complications, imaging features and relevant differential diagnoses, and aneurysm management.

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images

AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.

Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells:A systematic review

BACKGROUND Adipose-derived stem cells(ADSCs)and the stromal vascular fraction(SVF)have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions.Traditional enzymatic methods for isolating these cells face challenges such as high costs,lengthy processing time,and regulatory complexities.AIM This systematic review aimed to assess the efficacy and practicality of nonenzymatic,mechanical methods for isolating SVF and ADSCs,comparing these to conventional enzymatic approaches.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a comprehensive literature search was conducted across multiple databases.Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue.The risk of bias was assessed,and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies.RESULTS Nineteen studies met the inclusion criteria,highlighting various mechanical techniques such as centrifugation,vortexing,and ultrasonic cavitation.The review identified significant variability in cell yield and viability,and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures.Despite some advantages of mechanical methods,including reduced processing time and avoidance of enzymatic reagents,the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation.CONCLUSION Non-enzymatic,mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs,potentially simplifying the isolation process and reducing regulatory hurdles.However,further research is necessary to standardize these techniques and ensure consistent,high-quality cell yields for clinical applications.The development of efficient,safe,and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Construction and application of a three-dimensional vascular variation-based nephrometry scoring system for completely endophytic renal tumors

Background:Completely endophytic renal tumors(CERT)pose significant challenges due to their anatomical complexity and loss of visual clues about tumor location.A facile scoring model based on three-dimensional(3D)reconstructed images will assist in better assessing tumor location and vascular variations.Methods:In this retrospective study,80 patients diagnosed with CERT were included.Forty cases underwent preoperative assessment using 3D reconstructed imaging(3D-Cohort),while the remaining 40 cases were assessed using two-dimensional imaging(2D-Cohort).Vascular variations were evaluated by ascertaining the presence of renal arteries>1,prehilar branching arteries,and arteries anterior to veins.The proposed scoring system,termed RAL,encompassed three critical components:(R)adius(maximal tumor diameter in cm),(A)rtery(occurrence of arterial variations),and(L)ocation relative to the polar line.Comparison of the RAL scoring system was made with established nephrometry scoring systems.Results:A total of 48(60%)patients exhibited at least one vascular variation.In the 2D-Cohort,patients with vascular variations experienced significantly prolonged operation time,increased bleeding volume,and extended warm ischemia time compared with those without vascular variations.Conversely,the presence of vascular vari-ations did not significantly affect operative parameters in the 3D-Cohort.Furthermore,the 2D-Cohort demon-strated a notable decline in both short-and long-term estimated glomerular filtration rate(eGFR)changes com-pared with the 3D-Cohort,a trend consistent across patients with warm ischemia time≥25 min and those with vascular variations.Notably,the 2D-Cohort exhibited a larger margin of normal renal tissue compared with the 3D-Cohort.Elevated RAL scores correlated with larger tumor size,prolonged operation time,extended warm is-chemia time,and substantial postoperative eGFR decrease.The RAL scoring system displayed superior predictive capabilities in assessing postoperative eGFR changes compared with conventional nephrometry scoring systems.Conclusions:Our proposed 3D vascular variation-based nephrometry scoring system offers heightened proficiency in preoperative assessment,precise prediction of surgical complexity,and more accurate evaluation of postoper-ative renal function in CERT patients.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

QTL Analysis of Rice Peduncle Vascular Bundle System and Panicle Traits

A double haploid (DH) population of rice (Oryza sativa L.) derived from anther culture of ZYQ8/JX17, a typical indica and japonica hybrid, was used for genetic analysis of rice peduncle vascular system and panicle traits. The number of large vascular bundles (LVB), the number of small vascular bundles (SVB) in the peduncle, and the panicle traits including the number of primary rachis branches (PRB), the number of spikelets per panicle (SNP), peduncle top diameter (PTD), and panicle length (PL) were investigated in the parents and DH lines. The quantitative trait loci (QTLs) for each trait were analyzed based on the constructed molecular linkage map of this population. Three QTLs for LVB (qLVB_1, qLVB_6 and qLVB_7) were detected on chromosomes 1, 6, and 7, respectively. Two putative QTLs for SVB (qSVB_4 and qSVB_6) were mapped on chromosomes 4 and 6 respectively. Four QTLs (qPRB_4a, qPRB_4b, qPRB_6 and qPRB_7) on chromosomes 4, 6, and 7, respectively, were detected for PRB. Three QTLs (qSPN_4a, qSPN_4b and qSPN_6) were identified on chromosomes 4 and 6, respectively, which could significantly affect SPN. Five QTLs for PTD (qPTD_2, qPTD_5, qPTD_6, qPTD_8 and qPTD_12) were identified on chromosomes 2, 5, 6, 8, and 12, respectively. Three QTLs for PL (qPL_4, qPL_6 and qPL_8) were detected on chromosomes 4, 6, and 8, respectively. Clustering of QTLs, such as qLVB_6, qSVB_6, qSNP_6, qPTD_6, and qPL_6 detected in the interval G122_G1314b on chromosome 6, was found. These results suggest that some QTLs for peduncle vascular bundle system are possibly responsible for the panicle traits.

The plant vascular systemⅠ:From resource allocation,inter-organ communication and defense,to evolution of the monocot cambium

In recent years, considerable attention has been paid to exploring the complex gene regulatory networks involved in the development of the plant vascular system. Such information is crucial to our understanding of the molecular and cellular events which give rise to the integrated tissues of the xylem and phloem, leading to the formation of structurally continuous conduits that interconnect various organs of the plant. Vascular development begins in the embryo to form progenitor cells, and upon germination, these progenitor cells and their decedents in the shoot and root meristems will form phloem and xylem, and the cambium.

Modeling Thermal Regulation in Thin Vascular Systems:A Mathematical Analysis

Mimicking vascular systems in living beings,designers have realized microvascular composites to achieve thermal regulation and other functionalities,such as electromagnetic modulation,sensing,and healing.Such material systems avail circulating fluids through embedded vasculatures to accomplish the mentioned functionalities that benefit various aerospace,military,and civilian applications.Although heat transfer is a mature field,control of thermal characteristics in synthetic microvascular systems via circulating fluids is new,and a theoretical underpinning is lacking.What will benefit designers are predictive mathematical models and an in-depth qualitative understanding of vascular-based active cooling/heating.So,the central focus of this paper is to address the remarked knowledge gap.First,we present a reduced-order model with broad applicability,allowing the inlet temperature to differ from the ambient temperature.Second,we apply mathematical analysis tools to this reduced-order model and reveal many heat transfer properties of fluid-sequestered vascular systems.We derive point-wise properties(minimum,maximum,and comparison principles)and global properties(e.g.,bounds on performance metrics such as the mean surface temperature and thermal efficiency).These newfound results deepen our understanding of active cooling/heating and propel the perfecting of thermal regulation systems.

The plant vascular system Ⅱ:From resource allocation,inter-organ communication and defense,to evolution of the monocot cambium

In this Special Issue, a focus is placed on the role of the xylem as an essential conduit for the long-distance delivery of water and mineral nutrients from the soil to the vegetative （above-ground） regions of the plant. Xylem cells destined to form tracheids or vessel members, which will make up the conduit for this water and mineral transport from the roots to the shoots, undergo apoptosis, a process of programmed cell death.

The Plant Vascular System: Evolution, Development and Functions

The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system. In this review, we first examine the evolutionary events that gave rise to the tracheophytes, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms. The two essentialfunctions performed by the vascular system, namely the delivery of resources （water, essential mineral nutrients, sugars and amino acids） to the various plant organs and provision of mechanical support are next discussed. Here, we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem. Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental, physiological and defense-related processes, at the whole-plant level. A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology. Finally, areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.

Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.

Expression of thymidine kinase mediated by a novel non-viral delivery system under the control of vascular endothelial growth factor receptor 2 promoter selectively kills human umbilical vein endothelial cells

AIM: To investigate the killing efficiency of a recombinant plasmid containing a thymidine kinase (TK) domain insert driven by the vascular endothelial growth factor receptor 2 (VEGFR2) promoter (KDR) on vascular endothelial cells.METHODS: The KDR-TK fragment was extracted from pBluescript Ⅱ KDR-TK plasmid by enzymatic digestion with Xho I and Sal I. The enhanced green fluorescence protein (EGFP) carrier was extracted from pEGFP by the same procedure. The KDR-TK was inserted into the pEGFP carrier to construct pEGFP-KDR-TK. Using ultrasound irradiation and microbubble, pEGFP-KDR-TK was transferred into human umbilical vein endothelial cells (HUVECs). The transient infection rate was estimated by green fluorescent protein (GFP) expression. Transfected HUVECs, non-transfected HUVECs, and HepG2 cells were cultured in the presence of different concentrations of ganciclovir (GCV), and the killing efficacy of HSV-TK/GCV was analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The recombinant pEGFP-KDR-TK was successfully constructed by inserting the KDR-TK fragment into the pEGFP carrier. Transfected HUVECs showed cytoplasmic green fluorescence, and the transient transfection rate was about 20.3%. Pools of G418-resistant cells exhibited a higher sensitivity to theprodrug/GCV compared to non-transfected HUVECs or non-transfected HepG2 cells, respectively. CONCLUSION: KDR promoter and the suicide gene/prodrug system mediated by diagnostic ultrasound combined with microbubble can significantly kill HUVECs. Such therapy may present a novel and attractive approach to target gene therapy on tumor vessels.

Laparoscopic vs open complete mesocolic excision with central vascular ligation for colon cancer: A systematic review and meta-analysis

AIM To compare the effectiveness of laparoscopic complete mesocolic excision (CME) with central vascular ligation (L-CME) with its open (O-CME) counterpart. METHODS We conducted an electronic search of the PubMed/MEDLINE, Excerpta Medica Database, Web of Science Core Collection, Cochrane Center Register of Controlled Trails, Cochrane Database of Systematic Reviews, SciELO, and Korean Journal databases from their inception until May 2017. We considered randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that included patients with colonic cancer comparing L-CME and O-CME. Primary outcomes included the quality of the resected specimen (lymph nodes retrieved, complete mesocolic plane excision, tumor to arterial high tie, resected mesocolon surface). Secondary outcomes included the three-year and five-year overall and disease-free survival rates, recurrence of the disease, surgical data, and postoperative morbidity and mortality. Two authors of the review screened the methodological quality of the eligible trials and independently extracted data from individual studies. RESULTS A total of one RCT and eleven CCTs (four from Europe and seven from Asia) met the inclusion criteria for the current meta-analysis. These studies involved 1619 patients in L-CME and 1477 patients in O-CME. The L-CME was associated with the same quality of the resected specimen, with no differences regarding the retrieved lymphnodes (MD = -1.06, 95%CI: -3.65 to 1.53, P = 0.42), and tumor to high tie distance (MD = 14.26 cm, 95%CI: -4.30 to 32.82, P = 0.13); the surface of the resected mesocolon was higher in the L-CME group (MD = 11.75 cm2, 95%CI: 9.50 to 13.99, P < 0.001). The L-CME was associated with a lower rate of blood transfusions (OR = 0.45, 95%CI: 0.27 to 0.75, P = 0.002), faster recovery of gastrointestinal function, and less postoperative overall complication rate. The L-CME approach was associated with a statistical significant better three-year overall (OR = 2.02, 95%CI: 1.31 to 3.12, P = 0.001, I2 = 28%) and disease-free (OR = 1.45, 95% CI: 1.00 to 2.10, P = 0.05, I2 = 0%) survival. CONCLUSION The laparoscopic approach offers the same quality of the resected specimen as the open approach in complete mesocolic excision with central vascular ligation for colon cancer. The laparoscopic complete mesocolic excision with central vascular ligation is superior in all perioperative results and at least non-inferior in long-term oncological outcomes.