Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity...Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.展开更多
Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-en...Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.展开更多
Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood ve...Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.展开更多
Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of nov...Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.展开更多
Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells wer...Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).展开更多
Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor...Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.展开更多
AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of...AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.展开更多
BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment ep...BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.展开更多
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 sys...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.展开更多
Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic mac...The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).展开更多
Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substa...Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.展开更多
Natural silk from Bombyx mori has been used as medical sutures for several decades,and regenerated silk fibroin( RSF)based biomaterials have been increasingly studied in the past thirty years. However,vascular graft d...Natural silk from Bombyx mori has been used as medical sutures for several decades,and regenerated silk fibroin( RSF)based biomaterials have been increasingly studied in the past thirty years. However,vascular graft derived from silk fibroin fiber has been explored in recent several years with development of textile science and engineering. Moreover,endothelialization of vascular graft has been seen as an ideal strategy for preventing thrombosis and getting higher patency in a long term. Therefore,in the present work silk fibroin fiber vascular graft( SF) was chemically grafted with bioactive molecules such as heparin and RSF to improve the cytocompatibility. 3-aminopropyl-triethoxysilane(APTES),1-ethyl-3-(3-dimethylaminopropyl) carbodiie hydrochlide( EDC · HCl),and N-hydroxysuccinimide( NHS) have been employed as coupling agent and crosslinking agents,respectively. Microscopy and ATRFTIR were used to characterize the surface changes and the structure of the grafts after treatment,respectively. Cell culture in vitro and MTT assay were conducted to determine the improvement of cell affinity to the graft. Furthermore,mechanical properties of the grafts before and after treatment were compared. The results showed that the chemical grafting was an effective method for improving the cytocompatibility of SF without significant loss of mechanical properties.展开更多
Chronic pancreatitis is a chronic fibro-inflammatory disorder of the pancreas,resulting in recurrent abdominal pain,diabetes mellitus,and malnutrition.It may lead to various other complications such as pseudocyst form...Chronic pancreatitis is a chronic fibro-inflammatory disorder of the pancreas,resulting in recurrent abdominal pain,diabetes mellitus,and malnutrition.It may lead to various other complications such as pseudocyst formation,benign biliary stricture,gastric outlet obstruction;and vascular complications like venous thrombosis,variceal and pseudoaneurysmal bleed.Development of varices is usually due to chronic venous thrombosis with collateral formation and variceal bleeding can easily be tackled by endoscopic therapy.Pseudoaneurysmal bleed can be catastrophic and requires radiological interventions including digital subtraction angiography followed by endovascular obliteration,or sometimes with a percutaneous or an endoscopic ultrasound-guided approach in technically difficult situations.Procedure-related bleed is usually venous and mostly managed conservatively.Procedure-related arterial bleed,however,may require radiological interventions.展开更多
Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endot...Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.展开更多
The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared...The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.展开更多
Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of v...Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A(VEGF-A)in immature human fetal retinal microvascular endothelial cells(hfRMECs).Methods:Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques,including transmission electron microscopy,nanoparticle tracking analysis,bicinchoninic acid assays,and western blotting.The hfRMECs were identified using von Willebrand factor(vWF)co-staining and divided into four groups:a control group cultured under normoxic condition,a hypoxic model group,a hypoxic group treated with low-concentration hucMSC-Exos(75μg/mL)and a hypoxic group treated with high-concentration hucMSC-Exos(100μg/mL).Cell viability and proliferation were assessed using Cell Counting Kit-8(CCK-8)assay and EdU(5-ethynyl-2′-deoxyuridine)assay respectively.Expression levels of VEGF-A were evaluated using RT-PCR,western blotting and immunofluorescence.Results:Hypoxia significantly increased hfRMECs’viability and proliferation by upregulating VEGF-A levels.The administration of hucMSC-Exos effectively reversed this response,with the high-concentration group exhibiting greater efficacy compared to the lowconcentration group.Conclusion:In conclusion,hucMSC-Exos can dose-dependently inhibit hypoxia-induced hyperproliferation and VEGF-A overexpression in immature fetal retinal microvascular endothelial cells.展开更多
Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contr...Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.展开更多
Malignant mesenchymal tumors (MTM) in children represent 5% to 10% of malignant tumors in children. They constitute a heterogeneous group of tumors of various differentiations depending on their supposed tissue of ori...Malignant mesenchymal tumors (MTM) in children represent 5% to 10% of malignant tumors in children. They constitute a heterogeneous group of tumors of various differentiations depending on their supposed tissue of origin. They mainly include tumors of muscular origin, those derived from connective, vascular, nervous, or adipose tissue. Rhabdomyosarcoma (RMS) is the most common mesenchymal tumor in children and adolescents (60% to 70% of them). And it accounts for 5.8% of all malignant solid tumors in children. Almost half of rhabdomyosarcomas occur in the head and neck. The prognosis for this type of tumor is particularly poor. A case of rhabdomyosarcoma in the mandible with extension to the abdominal wall and unilateral testis in a 6-month-old infant is reported with evolution since birth. It is a purplish lesion at the level under the right chin which was initially taken for vascular malformation, evolving very quickly towards a mandibular mass deforming the painful face with inflammatory signs, followed by the appearance of a hard swelling under the skin on the left flank taking on the same aspect of the mandibular mass. This observation illustrates the need to know how to systematically think about tumor causes in the face of atypical aspects and to carry out an anatomopathological examination.展开更多
Laparoscopic cholecystectomy is one of the most frequently performed procedures in gastrointestinal surgery worldwide.Bleeding complications due to vascular injuries represent an important cause of morbidity and morta...Laparoscopic cholecystectomy is one of the most frequently performed procedures in gastrointestinal surgery worldwide.Bleeding complications due to vascular injuries represent an important cause of morbidity and mortality,especially when facing major bleeding during laparoscopy,where bleeding control can be technically challenging in inexperienced hands.Interestingly,the reported incidence rate of conversion to open surgery due to vascular lesions is approximately 0%-1.9%,with a mortality rate of approximately 0.02%.The primary aim of this article was to perform an up-to-date overview regarding the incidence and surgical management of vascular injuries during laparoscopic cholecystectomy according to the available scientific evidence.展开更多
基金supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065),the Innovation Groups of NSFC(81721001),and the Young Scientists Fund(82102279).
文摘Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
文摘Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.
文摘Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.
文摘Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.
基金supported by the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)the Key Basic Research Projects of the Foundation Strengthening Plan(2022-JCJQZD-096-00)+2 种基金the National Key Research and Development Program of China(2022YFA1104604)the National Natural Science Foundation of China(32000969)the Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).
基金supported by the Qingdao Medical Research Guidance Plan(2020-WJZD049).
文摘Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.
基金Supported by the National Natural Science Foundation of China(No.82101087)Shanghai Clinical Research Key Project(No.SHDC2020CR6029).
文摘AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.
基金The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
文摘BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.
基金This study was approved by Ethical Committee of The Sapienza University of Rome(5068/2018).
文摘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.
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
基金supported by Science and Technology Research Project of Jilin Provincial Department of Education,No.JJKH20220072KJ(to XL)Science and Technology Development Program of Jilin Province,No.20200201495JC(to YL)。
文摘The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).
基金financially supported by Natural Science Foundation of Shandong Province(No.ZR2023QH037)Medical and Health Science and Technology Development Program of Shandong Province(No.202203010622)+1 种基金GuangDong Basic and Applied Basic Research Foundation(No.2020A1515111005)China Postdoctoral Science Foundation(No.2018M643053).
文摘Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.
基金National Natural Science Foundations of China(No.51003014,No.31100682)"111 Project" Biomedical Textile Materials Science and Technology of China(No.B07024)
文摘Natural silk from Bombyx mori has been used as medical sutures for several decades,and regenerated silk fibroin( RSF)based biomaterials have been increasingly studied in the past thirty years. However,vascular graft derived from silk fibroin fiber has been explored in recent several years with development of textile science and engineering. Moreover,endothelialization of vascular graft has been seen as an ideal strategy for preventing thrombosis and getting higher patency in a long term. Therefore,in the present work silk fibroin fiber vascular graft( SF) was chemically grafted with bioactive molecules such as heparin and RSF to improve the cytocompatibility. 3-aminopropyl-triethoxysilane(APTES),1-ethyl-3-(3-dimethylaminopropyl) carbodiie hydrochlide( EDC · HCl),and N-hydroxysuccinimide( NHS) have been employed as coupling agent and crosslinking agents,respectively. Microscopy and ATRFTIR were used to characterize the surface changes and the structure of the grafts after treatment,respectively. Cell culture in vitro and MTT assay were conducted to determine the improvement of cell affinity to the graft. Furthermore,mechanical properties of the grafts before and after treatment were compared. The results showed that the chemical grafting was an effective method for improving the cytocompatibility of SF without significant loss of mechanical properties.
文摘Chronic pancreatitis is a chronic fibro-inflammatory disorder of the pancreas,resulting in recurrent abdominal pain,diabetes mellitus,and malnutrition.It may lead to various other complications such as pseudocyst formation,benign biliary stricture,gastric outlet obstruction;and vascular complications like venous thrombosis,variceal and pseudoaneurysmal bleed.Development of varices is usually due to chronic venous thrombosis with collateral formation and variceal bleeding can easily be tackled by endoscopic therapy.Pseudoaneurysmal bleed can be catastrophic and requires radiological interventions including digital subtraction angiography followed by endovascular obliteration,or sometimes with a percutaneous or an endoscopic ultrasound-guided approach in technically difficult situations.Procedure-related bleed is usually venous and mostly managed conservatively.Procedure-related arterial bleed,however,may require radiological interventions.
基金supported by Key Research and Development Plan of Xuzhou Science and Technology Bureau,No.KC21162(to XMZ)a grant from Jiangsu Key Laboratory of Brain Disease Bioinformationg,No.XZSYSKF2021018(to XMZ)+1 种基金Natural Science Fund for Colleges and Universities in Jiangsu Province,No.19KJB320024(to HNY)the Science and Technology Development Fund from Affiliated Hospital of Xuzhou Medical University,Nos.XYFM2021024(to XMZ),XYFM2021006(to DH).
文摘Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.
文摘The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.
基金supported by the following funds:1.Medical Scientific Research Foundation of Guangdong Province(A2022221)Natural Science Foundation of Guangdong Province(2019A1515011417)+2 种基金National Natural Science Foundation of China(81970806,82271094)Science and Technology Projects in Guangzhou(202201020030,202201020015)Guangdong High-Level Hospital Construction Fund(ynkt2021-zz16).
文摘Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A(VEGF-A)in immature human fetal retinal microvascular endothelial cells(hfRMECs).Methods:Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques,including transmission electron microscopy,nanoparticle tracking analysis,bicinchoninic acid assays,and western blotting.The hfRMECs were identified using von Willebrand factor(vWF)co-staining and divided into four groups:a control group cultured under normoxic condition,a hypoxic model group,a hypoxic group treated with low-concentration hucMSC-Exos(75μg/mL)and a hypoxic group treated with high-concentration hucMSC-Exos(100μg/mL).Cell viability and proliferation were assessed using Cell Counting Kit-8(CCK-8)assay and EdU(5-ethynyl-2′-deoxyuridine)assay respectively.Expression levels of VEGF-A were evaluated using RT-PCR,western blotting and immunofluorescence.Results:Hypoxia significantly increased hfRMECs’viability and proliferation by upregulating VEGF-A levels.The administration of hucMSC-Exos effectively reversed this response,with the high-concentration group exhibiting greater efficacy compared to the lowconcentration group.Conclusion:In conclusion,hucMSC-Exos can dose-dependently inhibit hypoxia-induced hyperproliferation and VEGF-A overexpression in immature fetal retinal microvascular endothelial cells.
基金Program of Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Natural Science Foundation of Shanghai,Grant/Award Number:201409004100 and 21ZR1453800+1 种基金Three Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,Grant/Award Number:SHDC2020CR6016-002 and SHDC2020CR4021Program of Shanghai Pulmonary Hospital,Grant/Award Number:fkzr2320 and FKLY20005。
文摘Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.
文摘Malignant mesenchymal tumors (MTM) in children represent 5% to 10% of malignant tumors in children. They constitute a heterogeneous group of tumors of various differentiations depending on their supposed tissue of origin. They mainly include tumors of muscular origin, those derived from connective, vascular, nervous, or adipose tissue. Rhabdomyosarcoma (RMS) is the most common mesenchymal tumor in children and adolescents (60% to 70% of them). And it accounts for 5.8% of all malignant solid tumors in children. Almost half of rhabdomyosarcomas occur in the head and neck. The prognosis for this type of tumor is particularly poor. A case of rhabdomyosarcoma in the mandible with extension to the abdominal wall and unilateral testis in a 6-month-old infant is reported with evolution since birth. It is a purplish lesion at the level under the right chin which was initially taken for vascular malformation, evolving very quickly towards a mandibular mass deforming the painful face with inflammatory signs, followed by the appearance of a hard swelling under the skin on the left flank taking on the same aspect of the mandibular mass. This observation illustrates the need to know how to systematically think about tumor causes in the face of atypical aspects and to carry out an anatomopathological examination.
文摘Laparoscopic cholecystectomy is one of the most frequently performed procedures in gastrointestinal surgery worldwide.Bleeding complications due to vascular injuries represent an important cause of morbidity and mortality,especially when facing major bleeding during laparoscopy,where bleeding control can be technically challenging in inexperienced hands.Interestingly,the reported incidence rate of conversion to open surgery due to vascular lesions is approximately 0%-1.9%,with a mortality rate of approximately 0.02%.The primary aim of this article was to perform an up-to-date overview regarding the incidence and surgical management of vascular injuries during laparoscopic cholecystectomy according to the available scientific evidence.
