AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a u...AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center,strongly associated with H pylori infection.The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS:We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls.A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM- 1 and integrin β7.In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated.We also performed immunostaining with anti-CD20,CD4,CD8 and CD68 antibodies to determine the lymphocyte subsets co- expressing integrin β7. RESULTS:Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection.Of note,the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls.Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates.Integrin β7-expressing mononuclear cells,mainly composed of CD20 and CD4 lymphocytes,were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM一1/ integrin a4p7 homing system may participate in gastric inflammation in response to H py/o}i-infection and contributes to MALT formation, typically leading to the development of NG.展开更多
Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel...Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.展开更多
Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may ...Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.展开更多
Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)in...Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.展开更多
Objective:To observe the clinical effect and protection of vascular endothelium of Zhixin-kang Capsule (ZXKC) in middle-aged and old people with unstable effort angina and hyperlipidemia. Methods: Sixty-five patients ...Objective:To observe the clinical effect and protection of vascular endothelium of Zhixin-kang Capsule (ZXKC) in middle-aged and old people with unstable effort angina and hyperlipidemia. Methods: Sixty-five patients with unstable effort angina were randomly divided into ZXKC group (34 cases) and control group (31 cases). Conventional western medical therapy was given to both groups, with ZXKC group receiving additional ZXKC treatment. Data of 20 healthy persons were taken as normal group. Forty-eight patients with hyperlipidemia were divided into ZXKC group treated with ZXKC (31 cases) and control group treated with Yixintong (17 cases). The changes of clinical symptoms and laboratory indexes in all the patients were observed before and after treatment. Results: In patients with unstable effort angina, the efficacy of treatment of ZXKC, the withdrawal rate of nitroglycerin, the relieving of symptoms, the improvement of the electrocardiogram, the counts of circulating endothelial cells, the content of platelet P-selectin, the content of plasma endothelin (ET), the activity of superoxide dismutase (SOD) and the activity of malonyldialdehyde (MDA) were all better than those in the control group. In patients with hyperlipidemia, there was no significant difference in lipids reduction between ZXKC group and the control group. In both groups, the total cholesterol (TC), triglyceride (TG), low density lipo-protein-cholesterol (LDL-C), lipoprotein(a) [Lp(a)] , ET, oxidized low density lipoprotein, MDA, arte-riosclerotic index (AI) all lowered obviously, while the SOD, HDL-C and calcitonin gene-related peptide (CGRP) were all elevated markedly. In the ZXKC group, the nitric oxide(NO) increased significantly whereas the ET/CGRP and ET/NO decreased markedly. The total effective rate in symptom relieving, the markedly effective rate, the reduction of TC, ET and ET/CGRP, and the elevation of SOD in ZXKC group were all superior to those in the control group. Conclusion: ZXKC could effectively resist myocardial ischemia, relieve angina, reduce blood lipids, protect vascular endothelial cells, inhibit the activation of platelets, and resist lipid peroxidation.展开更多
Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and reco...Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.展开更多
Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 8...Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.展开更多
Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Me...Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.展开更多
Epidemiological studies have found that the risk for cardiovascular disease is increased in patients with epilepsy. The Renin Angiontensin System (RAS), an important player in vascular tone control, is also involved i...Epidemiological studies have found that the risk for cardiovascular disease is increased in patients with epilepsy. The Renin Angiontensin System (RAS), an important player in vascular tone control, is also involved in many neurological disorders, including seizures and epilepsy. Although it has been reported that Angiotensin II (Ang II) release and Angiotensin receptors expression are altered in many cerebral areas in patients/animal models with neurological disorders, there are no data on the vascular function. We evaluated Ang I and Ang II-mediated vascular responses and to correlate their contractile responses to the pres- ence of endothelium and the protein levels of components of the RAS (AT1, AT2, Mas and ACE) in aorta isolated from genetically epileptic rats (WAR strain). The major finding was that the vascular contractile response induced by Ang I and Ang II is endothelium-dependent. Ang II induced contractions in aortas from Wistar rats either with intact endothelium (E+) (1.16 ± 0.04 g, n = 6) and endothelium-denuded (E-) (1.24 ± 0.04 g, n = 6). Maximum contractile response (ME) induced by Ang I was lower in Wistar E+ (0.45 ± 0.03 g, n = 6) compared with Wistar E- (1.13 ± 0.08 g, n = 6). Ang I and Ang II failed to induce contraction in WAR E+, whereas the ME induced by Ang I in WAR E- was lower (0.52 ± 0.04 g, n = 11) than in the Wistar. ME induced by Ang II in aortas from WAR was also lower (0.40 ± 0.03 g, n = 11) compared with Wistar. AT1 receptor expression in both E+ WAR and Wistar was lower than in both E- WAR and Wistar. AT2 and Mas receptor expression was higher in Wistar E- and E+ as compared to WAR E- and E+. ACE expression was higher in both E+ WAR and Wistar, but it was lower in both E- WAR and Wistar. Endothelium impairs the contractile response induced by Angiotensin in WAR, suggesting that endothelial relaxing factors play important role on the aorta contraction.展开更多
In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of M...In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.展开更多
BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more rese...BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.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
Osteogenesis imperfecta(OI)is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding typeⅠcollagen.While it is well known that ...Osteogenesis imperfecta(OI)is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding typeⅠcollagen.While it is well known that OI reflects defects in the activity of bone-forming osteoblasts,it is currently unclear whether OI also reflects defects in the many other cell types comprising bone,including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility.展开更多
AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induc...AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.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
AIM:To develop a deep learning-based model for automatic retinal vascular segmentation,analyzing and comparing parameters under diverse glucose metabolic status(normal,prediabetes,diabetes)and to assess the potential ...AIM:To develop a deep learning-based model for automatic retinal vascular segmentation,analyzing and comparing parameters under diverse glucose metabolic status(normal,prediabetes,diabetes)and to assess the potential of artificial intelligence(AI)in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes.METHODS:Retinal fundus photos from 200 normal individuals,200 prediabetic patients,and 200 diabetic patients(600 eyes in total)were used.The U-Net network served as the foundational architecture for retinal arteryvein segmentation.An automatic segmentation and evaluation system for retinal vascular parameters was trained,encompassing 26 parameters.RESULTS:Significant differences were found in retinal vascular parameters across normal,prediabetes,and diabetes groups,including artery diameter(P=0.008),fractal dimension(P=0.000),vein curvature(P=0.003),C-zone artery branching vessel count(P=0.049),C-zone vein branching vessel count(P=0.041),artery branching angle(P=0.005),vein branching angle(P=0.001),artery angle asymmetry degree(P=0.003),vessel length density(P=0.000),and vessel area density(P=0.000),totaling 10 parameters.CONCLUSION:The deep learning-based model facilitates retinal vascular parameter identification and quantification,revealing significant differences.These parameters exhibit potential as biomarkers for prediabetes and diabetes.展开更多
Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis...Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.展开更多
Background and Objective:The most feared complication of uncorrected secundum Atrial Septal Defect(ASD)is pulmonary arterial hypertension(PAH).Pulmonary vascular resistance(PVR)is crucial in detecting precapil-lary pu...Background and Objective:The most feared complication of uncorrected secundum Atrial Septal Defect(ASD)is pulmonary arterial hypertension(PAH).Pulmonary vascular resistance(PVR)is crucial in detecting precapil-lary pulmonary hypertension(PH)to guide the need for PAH-specific therapy.There is a change in the cut-off value of PVR according to the recently updated PH guideline.How echocardiographic PVR(PVRecho)correlates to PVR by right heart catheterization(RHC)(PVRcath)according to the new guidelines has not been known.The aim of this study is to determine the reliability of PVRecho in detecting PAH in Uncorrected Ostium Secundum ASD based on the current updated guideline and to help screen the high PVR group.Methods:429 ostium secun-dum ASD in the COngenital HeARt Disease in Adult and Pulmonary Hypertension(COHARD-PH)registry was divided into three groups according to the PVR.PVRecho was calculated using Abbas’Formula and compared the its gold standard,the PVRcath.The correlation between the two methods was analyzed.The Bland-Altman plot was used to analyze the agreement between the two methods.Receiver operating characteristics(ROC)analysis was used to determine the PVRecho cut-off value for high PVR.Results:The majority of the population(63.5%)had high PVR.Female gender dominated the study population(84%).PVR_(echo) was significantly correlated with PVRcath(r=0.6225,p<0.0001).Bland-Altman plot among all groups and in subgroups analysis showed a wide range of agreement.PVRecho underestimated PVRcath 5.124 WU.In subgroup analysis,PVRecho overestimated PVRcath 0.35 WU in those with PVR<2 WU.In the second and third groups,PVR_(echo) underestimated PVRcath 0.52 and 10.77 WU,respectively.Conclusion:PVRecho is reliable in predicting high PVR in uncorrected secun-dum ASD.However,there is a wide range of agreement.PVR_(echo) cut-off value of>1.62 WU showed good dis-criminatory power in determining high PVR.展开更多
The so-called fourth-generation biodegradable vascular stent has become a research hotspot in thefield of bioengineering because of its good degradation ability and drug-loading characteristics.However,the preparationo...The so-called fourth-generation biodegradable vascular stent has become a research hotspot in thefield of bioengineering because of its good degradation ability and drug-loading characteristics.However,the preparationof polymer-degraded vascular stents is affected by known problem such as poor processflexibility,low formingaccuracy,large diameter wall thickness,limited complex pore structure,weak mechanical properties of radial support and high process cost.In this study,a deposition technique based on a high-voltage electric-field-driven continuous rotating jet is proposed to fabricate fully degraded polymer vascular stents.The experimental results showthat,due to the rotation of the deposition axis,the deposition direction of PCL(polycaprolactone)micro-jet isalways tangent to the surface of the deposition axis.The direction of the viscous drag force is also consistent withthe deposition direction of the jet.It is shown that by setting different rotation speeds of deposition axisωandlinear motion speeds of the nozzle V,the direction of rotation,pitch and angle of the individual printed spiralcurve can be precisely tuned.In the process of multiple spiral curves matching the deposition forming thin walltube mesh,the mesh shape and size of the thin wall tube can be accurately controlled by changing the number ofmatching spiral curves and the size of the matching position bias distance.Finally,the characteristics of a PCLtubular stent sample(with uniform-size microfibers and mesh shape),fabricated under the appropriate processparameters are described in detail.展开更多
文摘AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center,strongly associated with H pylori infection.The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS:We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls.A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM- 1 and integrin β7.In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated.We also performed immunostaining with anti-CD20,CD4,CD8 and CD68 antibodies to determine the lymphocyte subsets co- expressing integrin β7. RESULTS:Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection.Of note,the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls.Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates.Integrin β7-expressing mononuclear cells,mainly composed of CD20 and CD4 lymphocytes,were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM一1/ integrin a4p7 homing system may participate in gastric inflammation in response to H py/o}i-infection and contributes to MALT formation, typically leading to the development of NG.
基金funded by Beijing Science and Technology Commission Foundation[Z151100004015071]
文摘Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.
基金Supported by The Fundo de Incentivo à Pesquisa e Eventos(FIPE)at Hospital de Clínicas de Porto Alegre,No.HCPA-120265
文摘Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.
基金the National Natural Science Foundation of China(Nos.81560589,30960450,81173110 and 81560072)Yunnan Provincial Science and Technology Department(Nos.202105AF150015,202102AA310030,2018FE001(-026),2017FE467(-019),2014BC012,and 2017IC041)Yunnan Provincial Educational Department(Nos.2018JS161).
文摘Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.
基金This study was funded by Natural Science Foundation of Shandong Province (No. Y97C22058)
文摘Objective:To observe the clinical effect and protection of vascular endothelium of Zhixin-kang Capsule (ZXKC) in middle-aged and old people with unstable effort angina and hyperlipidemia. Methods: Sixty-five patients with unstable effort angina were randomly divided into ZXKC group (34 cases) and control group (31 cases). Conventional western medical therapy was given to both groups, with ZXKC group receiving additional ZXKC treatment. Data of 20 healthy persons were taken as normal group. Forty-eight patients with hyperlipidemia were divided into ZXKC group treated with ZXKC (31 cases) and control group treated with Yixintong (17 cases). The changes of clinical symptoms and laboratory indexes in all the patients were observed before and after treatment. Results: In patients with unstable effort angina, the efficacy of treatment of ZXKC, the withdrawal rate of nitroglycerin, the relieving of symptoms, the improvement of the electrocardiogram, the counts of circulating endothelial cells, the content of platelet P-selectin, the content of plasma endothelin (ET), the activity of superoxide dismutase (SOD) and the activity of malonyldialdehyde (MDA) were all better than those in the control group. In patients with hyperlipidemia, there was no significant difference in lipids reduction between ZXKC group and the control group. In both groups, the total cholesterol (TC), triglyceride (TG), low density lipo-protein-cholesterol (LDL-C), lipoprotein(a) [Lp(a)] , ET, oxidized low density lipoprotein, MDA, arte-riosclerotic index (AI) all lowered obviously, while the SOD, HDL-C and calcitonin gene-related peptide (CGRP) were all elevated markedly. In the ZXKC group, the nitric oxide(NO) increased significantly whereas the ET/CGRP and ET/NO decreased markedly. The total effective rate in symptom relieving, the markedly effective rate, the reduction of TC, ET and ET/CGRP, and the elevation of SOD in ZXKC group were all superior to those in the control group. Conclusion: ZXKC could effectively resist myocardial ischemia, relieve angina, reduce blood lipids, protect vascular endothelial cells, inhibit the activation of platelets, and resist lipid peroxidation.
文摘Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.
文摘Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.
文摘Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.
文摘Epidemiological studies have found that the risk for cardiovascular disease is increased in patients with epilepsy. The Renin Angiontensin System (RAS), an important player in vascular tone control, is also involved in many neurological disorders, including seizures and epilepsy. Although it has been reported that Angiotensin II (Ang II) release and Angiotensin receptors expression are altered in many cerebral areas in patients/animal models with neurological disorders, there are no data on the vascular function. We evaluated Ang I and Ang II-mediated vascular responses and to correlate their contractile responses to the pres- ence of endothelium and the protein levels of components of the RAS (AT1, AT2, Mas and ACE) in aorta isolated from genetically epileptic rats (WAR strain). The major finding was that the vascular contractile response induced by Ang I and Ang II is endothelium-dependent. Ang II induced contractions in aortas from Wistar rats either with intact endothelium (E+) (1.16 ± 0.04 g, n = 6) and endothelium-denuded (E-) (1.24 ± 0.04 g, n = 6). Maximum contractile response (ME) induced by Ang I was lower in Wistar E+ (0.45 ± 0.03 g, n = 6) compared with Wistar E- (1.13 ± 0.08 g, n = 6). Ang I and Ang II failed to induce contraction in WAR E+, whereas the ME induced by Ang I in WAR E- was lower (0.52 ± 0.04 g, n = 11) than in the Wistar. ME induced by Ang II in aortas from WAR was also lower (0.40 ± 0.03 g, n = 11) compared with Wistar. AT1 receptor expression in both E+ WAR and Wistar was lower than in both E- WAR and Wistar. AT2 and Mas receptor expression was higher in Wistar E- and E+ as compared to WAR E- and E+. ACE expression was higher in both E+ WAR and Wistar, but it was lower in both E- WAR and Wistar. Endothelium impairs the contractile response induced by Angiotensin in WAR, suggesting that endothelial relaxing factors play important role on the aorta contraction.
文摘In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
文摘BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.
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supported by the National Natural Science Foundation of China (81972034,92068104 and 82002262 to R.X.)the National Key R&D Program of China (2020YFA0112900 to R.X.)+5 种基金Project of Xiamen Cell Therapy Research Center (3502Z20214001 to R.X.)supported by a the NIH grant of US (R01AR075585,R01HD115274,R01CA282815 to M.B.G.)Career Award for Medical Scientists from the Burroughs Wellcome Funda Pershing Square Sohn Cancer Research Alliance and the Maximizing Innovation in Neuroscience Discovery (MIND)Prizesupported by a Jump Start Research Career Development Award from Weill Cornell Medicinea Study Abroad Scholarships from the Mogam Science Scholarship Foundation。
文摘Osteogenesis imperfecta(OI)is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding typeⅠcollagen.While it is well known that OI reflects defects in the activity of bone-forming osteoblasts,it is currently unclear whether OI also reflects defects in the many other cell types comprising bone,including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility.
基金Supported by the Xingtai Key Research and Development Projects (No.2022zz073)the Hebei Key Research and Development Projects (No.23377712D).
文摘AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.
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.
基金Supported by Shenzhen Science and Technology Program(No.JCYJ20220530153604010).
文摘AIM:To develop a deep learning-based model for automatic retinal vascular segmentation,analyzing and comparing parameters under diverse glucose metabolic status(normal,prediabetes,diabetes)and to assess the potential of artificial intelligence(AI)in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes.METHODS:Retinal fundus photos from 200 normal individuals,200 prediabetic patients,and 200 diabetic patients(600 eyes in total)were used.The U-Net network served as the foundational architecture for retinal arteryvein segmentation.An automatic segmentation and evaluation system for retinal vascular parameters was trained,encompassing 26 parameters.RESULTS:Significant differences were found in retinal vascular parameters across normal,prediabetes,and diabetes groups,including artery diameter(P=0.008),fractal dimension(P=0.000),vein curvature(P=0.003),C-zone artery branching vessel count(P=0.049),C-zone vein branching vessel count(P=0.041),artery branching angle(P=0.005),vein branching angle(P=0.001),artery angle asymmetry degree(P=0.003),vessel length density(P=0.000),and vessel area density(P=0.000),totaling 10 parameters.CONCLUSION:The deep learning-based model facilitates retinal vascular parameter identification and quantification,revealing significant differences.These parameters exhibit potential as biomarkers for prediabetes and diabetes.
基金sponsored by the National Natural Science Foundation of China (Nos.52235007, 52325504, T2121004)Zhejiang Province Natural Science Foundation of China under Grant No.LQ23H090012, LQ22H180001the Science and Technology of Medicine and Health program of Zhejiang Province (No.2023RC028)。
文摘Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.
文摘Background and Objective:The most feared complication of uncorrected secundum Atrial Septal Defect(ASD)is pulmonary arterial hypertension(PAH).Pulmonary vascular resistance(PVR)is crucial in detecting precapil-lary pulmonary hypertension(PH)to guide the need for PAH-specific therapy.There is a change in the cut-off value of PVR according to the recently updated PH guideline.How echocardiographic PVR(PVRecho)correlates to PVR by right heart catheterization(RHC)(PVRcath)according to the new guidelines has not been known.The aim of this study is to determine the reliability of PVRecho in detecting PAH in Uncorrected Ostium Secundum ASD based on the current updated guideline and to help screen the high PVR group.Methods:429 ostium secun-dum ASD in the COngenital HeARt Disease in Adult and Pulmonary Hypertension(COHARD-PH)registry was divided into three groups according to the PVR.PVRecho was calculated using Abbas’Formula and compared the its gold standard,the PVRcath.The correlation between the two methods was analyzed.The Bland-Altman plot was used to analyze the agreement between the two methods.Receiver operating characteristics(ROC)analysis was used to determine the PVRecho cut-off value for high PVR.Results:The majority of the population(63.5%)had high PVR.Female gender dominated the study population(84%).PVR_(echo) was significantly correlated with PVRcath(r=0.6225,p<0.0001).Bland-Altman plot among all groups and in subgroups analysis showed a wide range of agreement.PVRecho underestimated PVRcath 5.124 WU.In subgroup analysis,PVRecho overestimated PVRcath 0.35 WU in those with PVR<2 WU.In the second and third groups,PVR_(echo) underestimated PVRcath 0.52 and 10.77 WU,respectively.Conclusion:PVRecho is reliable in predicting high PVR in uncorrected secun-dum ASD.However,there is a wide range of agreement.PVR_(echo) cut-off value of>1.62 WU showed good dis-criminatory power in determining high PVR.
基金supported by the National Natural Science Foundation of China(Grant Nos.51305128 and 52005059)The Key Scientific and Technological Project of Henan Province(Grant Nos.242102231054 and 242102220073)The Provincial Graduate Quality Engineering Project(Grant No.YJS2024JD38)。
文摘The so-called fourth-generation biodegradable vascular stent has become a research hotspot in thefield of bioengineering because of its good degradation ability and drug-loading characteristics.However,the preparationof polymer-degraded vascular stents is affected by known problem such as poor processflexibility,low formingaccuracy,large diameter wall thickness,limited complex pore structure,weak mechanical properties of radial support and high process cost.In this study,a deposition technique based on a high-voltage electric-field-driven continuous rotating jet is proposed to fabricate fully degraded polymer vascular stents.The experimental results showthat,due to the rotation of the deposition axis,the deposition direction of PCL(polycaprolactone)micro-jet isalways tangent to the surface of the deposition axis.The direction of the viscous drag force is also consistent withthe deposition direction of the jet.It is shown that by setting different rotation speeds of deposition axisωandlinear motion speeds of the nozzle V,the direction of rotation,pitch and angle of the individual printed spiralcurve can be precisely tuned.In the process of multiple spiral curves matching the deposition forming thin walltube mesh,the mesh shape and size of the thin wall tube can be accurately controlled by changing the number ofmatching spiral curves and the size of the matching position bias distance.Finally,the characteristics of a PCLtubular stent sample(with uniform-size microfibers and mesh shape),fabricated under the appropriate processparameters are described in detail.
