Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of p...Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury.Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role.Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk.In this review,we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension,obstructive sleep-apnea syndrome,obesity,diabetes mellitus,peripheral arterial disease,coronary artery disease,pulmonary hypertension,and heart failure.Recent studies have introduced the novel concept that physical activity,either performed as a single exercise session or performed as part of an exercise training program,results in a significant increase of circulating EPCs.In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.展开更多
This study aims to examine the levels of circulating endothelial progenitor cells （cEPCs） in the peripheral blood of patients with non-Hodgkin lymphoma （NHL） and their correlation with the tumor stage. Forty-one p...This study aims to examine the levels of circulating endothelial progenitor cells （cEPCs） in the peripheral blood of patients with non-Hodgkin lymphoma （NHL） and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Pe- ripheral blood mononuclear cells （PBMCs） were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 （VEGFR-2, CD309） and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group （P=-0.000）. The cEPCs counts in patients with NHL of stage III-1V were significantly greater than in stage I -II （P=-0.010）. FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender （P=0.401） or the pathological category （P=0.852）. It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.展开更多
Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive...Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.展开更多
Objective: To observe the effect and clinical significance of circulating endothelial cells (CEC) in the pathogenesis of coronary heart disease with unstable angina pectoris (CHD-UAP), and to explore the protective ef...Objective: To observe the effect and clinical significance of circulating endothelial cells (CEC) in the pathogenesis of coronary heart disease with unstable angina pectoris (CHD-UAP), and to explore the protective effect of Chinese herbs for activating blood circulation, removing stasis and supplementing Qi (CH) on CHD-UAP patient's CEC. Methods: Sixty patients with diagnosis of CHD-UAP confirmed and differentiated to be Qi-deficiency and blood stasis by TCM were randomly divided into two groups and treated, on the basis of Western drug-therapy, with Tongxinluo capsule (通心络胶囊, TXL) and Huoxue Tongmai capsule (活血通脉胶囊, HXTM) respectively by way of oral taking three times a day, 3 capsules every time, with 1 month as one therapeutic course. The number of CEC in patients' blood circulation was counted before and after treatment. Besides, the number of CEC in 30 healthy persons was also counted for control. Results: The number of CEC in CHD-UAP patients was significantly higher than that in the healthy persons (P<0.01). After the patients were treated with CH, either TXL or HXTM, it significantly decreased (P<0.01)with insignificant difference between the two treated groups. Conclusion: CEC in CHD-UAP patients is severely damaged and endothelial function in disorder, Chinese herbs have protective effect on patients' CEC.展开更多
Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic resp...Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic responses of tumors,and thus,could be used as an indicator to predict the efficacy of tumor treatments.The purpose of this study was to investigate the correlation and impact of endothelial cells with and on the efficacy of first-line therapy(platinum-based or tyrosine kinase inhibitor drugs treatments)for advanced non-small-cell lung cancer.Methods:We analyzed 45 inpatients who met the inclusion criteria of diagnosis with inoperable non-small-cell lung cancer stages III and IV,in the People’s Hospital of Guangxi Zhuang Autonomous Region from January 2019 to January 2020.The flow cytometry technique was adopted to detect pretreatment levels of circulating endothelial cells in peripheral blood of patients with advanced non-small-cell lung cancer.The pretreatment peripheral blood was collected to analyze the relations of circulating endothelial cells with different clinical characteristics and efficacy.Results:The level of pretreatment circulating endothelial cells was significantly correlated with the efficacy of treatment(P<0.05)but irrelevant to the patient’s physical conditions,pathological type,tumor stage,and pretreatment serum carcinoembryonic antigen(P>0.05).The comparison between the groups of response(complete response+partial response)and nonresponse(stable disease+progressive disease)showed a significant difference in circulating endothelial cells count.Compared with low levels of circulating endothelial cells,a high level of circulating endothelial cells led to a poor efficacy(P<0.05).Conclusion:The level of pretreatment circulating endothelial cells significantly correlated with the efficiency of first-line therapy for non-small-cell lung cancer.Compared with low level of circulating endothelial cells,high level of circulating endothelial cells lead to poor efficacy.Therefore,circulating endothelial cell is indeed an effective indicator for predicting the efficacy of first-line therapy for advanced non-small-cell lung cancer.展开更多
BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endot...BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium.They also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and neovascularization.Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities.However,the effects of exercise on EPCs in different stages of CHF remain under investigation.AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different severity.METHODS Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle ergometer.Venous blood was sampled before and after CPET.Five circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated cells.RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:2(1-2)vs post CPET:3(2-5)cells/106 enucleated cells,P<0.001],while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:42(19-73)vs post CPET:90(39-118)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:2(1-3)vs post CPET:6(3-9)cells/106 enucleated cells,P<0.001],CD34+/CD133+/VEGFR2[pre CPET:10(7-18)vs post CPET:14(10-19)cells/106 enucleated cells,P<0.01],CD34+/CD45-/CD133-[pre CPET:218(158-247)vs post CPET:311(254-569)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:1(1-2)vs post CPET:4(2-6)cells/106 enucleated cells,P<0.001].A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak,ventilation/carbon dioxide output slope and EF as well(P<0.05).However,there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison(P>0.05).CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients,but this increase was not associated with syndrome severity.Further investigation,however,is needed.展开更多
BACKGROUND Acute respiratory distress syndrome(ARDS)is injury of alveolar epithelial cells and capillary endothelial cells caused by various factors,including endogenous and exogenous lung factors,leading to diffuse p...BACKGROUND Acute respiratory distress syndrome(ARDS)is injury of alveolar epithelial cells and capillary endothelial cells caused by various factors,including endogenous and exogenous lung factors,leading to diffuse pulmonary interstitial and alveolar edema,and acute respiratory failure.ARDS involves alveolar epithelial cells and pulmonary interstitial capillary endothelial cells.Circulating endothelial cells(CECs)are the only marker that directly reflects vascular endothelial injury in vivo.There have been few studies on the correlation between peripheral blood CECs and ARDS at home and abroad.The lungs are the organs with the highest capillary density and the most endothelial cells,thus,it is speculated that when ARDS occurs,CECs are stimulated and damaged,and released into the circulatory system.AIM To explore the correlation between CEC level and severity of ARDS in patients postoperatively.METHODS Blood samples were collected from all patients on day 2(d2)and day 5(d5)after surgery.The control group comprised 32 healthy volunteers.Number of CECs was measured by flow cytometry,and operation time was recorded.Changes in various indexes of patients were monitored,and diagnosis of ARDS was determined based on ARDS Berlin definition.We comprised d2 CECs in different groups,correlation between operation time and d2 CECs,ARDS of different severity by d2 CECs,and predictive value of d2 CECs for ARDS in postoperative patients.RESULTS The number of d2 CECs in the ARDS group was significantly higher than that in the healthy control group(P<0.001).The number of d2 CECs in the ARDS group was significantly higher than that in the non-ARDS group(P<0.001).The number of d2 CECs in the non-ARDS group was significantly higher than that in the healthy control group(P<0.001).Operation time was positively correlated with number of CECs on d2(rs=0.302,P=0.001).The number of d2 CECs in the deceased group was significantly higher than that in the improved group(P<0.001).There was no significant difference in number of d2 CECs between patients with mild and moderate ARDS.The number of d2 CECs in patients with severe ARDS was significantly higher than that in patients with mild and moderate ARDS(P=0.041,P=0.037).There was no significant difference in number of d5 and d2 CECs in the non-ARDS group after admission to intensive care.The number of d5 CECs was higher than the number of d2 CECs in the ARDS improved group(P<0.001).The number of d5 CECs was higher than the number of d2 CECs in the ARDS deceased group(P=0.002).If the number of CECs was>1351/mL,sensitivity and specificity of predicting ARDS were 80.8%and 78.1%,respectively.CONCLUSION Changes in number of CECs might predict occurrence and adverse outcome of ARDS after surgery,and higher numbers of CECs indicate worse prognosis of ARDS.展开更多
Background:Endometriosis(EM)is a complex benign gynecological disease,but it has malignant biological behavior and can invade any part of the body.Clinical manifestations include pelvic pain,dysmenorrhea,infertility,p...Background:Endometriosis(EM)is a complex benign gynecological disease,but it has malignant biological behavior and can invade any part of the body.Clinical manifestations include pelvic pain,dysmenorrhea,infertility,pelvic nodules,and masses.Our previous study successfully detected circulating endometrial cells(CECs)in the peripheral blood of patients with EM.The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method,to further accurately capture CECs,understand the characteristics of these cells,and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods:Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells(CVECs)was taken from EM patients(n=34)hospitalized in the Peking University People’s Hospital.We used the subtraction enrichment and immunostaining fluorescence in situ hybridization(SE-iFISH)method to exclude the interference of red blood cells,white blood cells,and CVECs,so as to accurately capture the CECs in the peripheral blood of patients with EM.Then we clarified the size and ploidy number of chromosome 8 of CECs,and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics.Results:The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH.Overall,34 eligible EM patients were enrolled.The results showed that the detection rates of CECs were 58.8%in EM patients and 16.7%in the control group.However,after classification according to clinical characteristics,more CECs could be detected in the peripheral blood of patients with rapidly progressive EM,with a detection rate of 94.4%(17/18).In total,63.5%(40/63)of these cells were small cells with diameters below 5μm,and 44.4%(28/63)were aneuploid cells.No significant association was found between the number of CECs and EM stage.Conclusion:The number and characteristics of CECs are related to the clinical course characteristics of patients with EM,such as pain and changes in lesion size,and may be used as biomarkers for personalized treatment and management of EM in the future.展开更多
OBJECTIVE: To study the ehanges of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation anti pancreatic microcirculation in rats with acut...OBJECTIVE: To study the ehanges of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation anti pancreatic microcirculation in rats with acute edematous pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: PECAM-I expression on PMNs showed no significant difference between pancreatic microcirculation and peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated, but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1 expression had a significant difference between pancreatic microcirculation and peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1 expression on PMNs is in a converse way between pancreatic microcirculation and peripheral circulation in AEP.展开更多
The number of the circulating angiogenic cells （CACs） and colony forming units （CFUs） derived from cultured circulating mononuclear cells （MNCs） represents a laboratory surrogate for endothelial cell repair abil...The number of the circulating angiogenic cells （CACs） and colony forming units （CFUs） derived from cultured circulating mononuclear cells （MNCs） represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction （ED） and vascular risk factors （VRFs） showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4weeks of treatment with tadalafil （20 mg every other day） or with a placebo. The tadalafil treatment improved erectile function （P = 0.0028）, but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 （P = 0.011） and tissue type plasminogen activator （P = 0.005） were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.展开更多
Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunoc...Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunocompromised or previously irradiated patients. These are part of a spectrum of more aggressive fibro-histiocytic neoplasms. In the older literature, these have been termed aggressive or metastatic AFX, but currently these have been reclassified as pleomorphic dermal sarcomas (PDS) and systemic undifferentiated pleomorphic sarcoma (UPS, formerly malignant fibrohistiocytic sarcoma, MFH). We present the case of a 64-year old woman who developed a deeply invasive PDS on the vertex of her scalp invading to the galea, with in-transit scalp metastases. Very little information is available about optimal treatment of metastatic PDS lesions. The patient was initially treated with 2 cycles of epirubicin/ifosfamide chemotherapy, resulting in life-threatening complications. A pretreatment peripheral blood sample was sent for CTC-derived colony assay. This sample grew 8 colonies from 10 ml blood. The tumor failed to respond to epirubicin and ifosfamide, and after several months of hospitalization, a second peripheral blood CTC-derived colony assay grew >376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to function as a potential prognostic marker.展开更多
Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cell...Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cells(CECs).Methods:Cell morphology was determined using a circularity index(4π×area/perimeter2)for each CECs population extracted from surgical FECD specimens(N=2)and healthy Eye bank corneas(N=3).CECs were cultured 28 days post-confluency.Supernatant was collected and analysed using Proteome Profiler Array detecting 35 proteases and 32 PIs(R&D Systems).Proteome signal was analyzed using Image Studio Lite and correlated with the population’s circularity index.Results:Calculation of circularity index reported different morphologies among FECD populations(0.59±0.18 and 0.64±0.17)and healthy populations(0.44±0.18,0.66±0.13 and 0.71±0.11).Proteome arrays revealed the presence of 10 proteases(ADAMTS1,Cathepsin A,B,D,and X/Z/P,DPPIV/CD26,MMP-2,3 and 12,uPA/Urokinase)and 10 PIs(Protease Nexin II,Cystatin B and C,EMMPRIN/CD147,Latexin,Lipocalin-1,Serpin E1,TFPI,TFPI-2,TIMP-1,2 and 4).Healthy and FECD specimens showed similar variation patterns according to morphology for secretion of ADAMTS1,MMP-3 and 12.However,opposing patterns between healthy and FECD populations were observed for Cathepsin B and D.Moreover,some proteins did not show variation according to phenotype in healthy CECs,but did in FECD CECs:Cathepsin A,Cystatin C,TFPI-2 and total TIMPs.For the other proteins,secretion did not vary according to morphology or no specific pattern was distinguishable.Conclusions:To conclude,our results suggest that cell phenotype is linked to the secretion of certain proteases/PIs in both groups.However,there seems to be differences in secretion of particular proteases and PIs between FECD and healthy specimens as morphology did not have a similar influence.These differences might initiate an imbalance between proteases and PIs explaining the irregular thickening of the Descemet membrane seen in FECD.展开更多
文摘Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury.Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role.Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk.In this review,we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension,obstructive sleep-apnea syndrome,obesity,diabetes mellitus,peripheral arterial disease,coronary artery disease,pulmonary hypertension,and heart failure.Recent studies have introduced the novel concept that physical activity,either performed as a single exercise session or performed as part of an exercise training program,results in a significant increase of circulating EPCs.In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.
基金supported by the National Natural Science Foundation of China(No.30900597)
文摘This study aims to examine the levels of circulating endothelial progenitor cells （cEPCs） in the peripheral blood of patients with non-Hodgkin lymphoma （NHL） and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Pe- ripheral blood mononuclear cells （PBMCs） were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 （VEGFR-2, CD309） and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group （P=-0.000）. The cEPCs counts in patients with NHL of stage III-1V were significantly greater than in stage I -II （P=-0.010）. FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender （P=0.401） or the pathological category （P=0.852）. It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.
基金Supported by Sciences and Technology Commission of Shanghai Municipality (08ZR1422100 and 08410701200)
文摘Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.
文摘Objective: To observe the effect and clinical significance of circulating endothelial cells (CEC) in the pathogenesis of coronary heart disease with unstable angina pectoris (CHD-UAP), and to explore the protective effect of Chinese herbs for activating blood circulation, removing stasis and supplementing Qi (CH) on CHD-UAP patient's CEC. Methods: Sixty patients with diagnosis of CHD-UAP confirmed and differentiated to be Qi-deficiency and blood stasis by TCM were randomly divided into two groups and treated, on the basis of Western drug-therapy, with Tongxinluo capsule (通心络胶囊, TXL) and Huoxue Tongmai capsule (活血通脉胶囊, HXTM) respectively by way of oral taking three times a day, 3 capsules every time, with 1 month as one therapeutic course. The number of CEC in patients' blood circulation was counted before and after treatment. Besides, the number of CEC in 30 healthy persons was also counted for control. Results: The number of CEC in CHD-UAP patients was significantly higher than that in the healthy persons (P<0.01). After the patients were treated with CH, either TXL or HXTM, it significantly decreased (P<0.01)with insignificant difference between the two treated groups. Conclusion: CEC in CHD-UAP patients is severely damaged and endothelial function in disorder, Chinese herbs have protective effect on patients' CEC.
基金This study was supported by Guangxi Medical and Health Appropriate Technology Development and Application Project(No.S2019075)Self-financed Program by Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z20180748).
文摘Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic responses of tumors,and thus,could be used as an indicator to predict the efficacy of tumor treatments.The purpose of this study was to investigate the correlation and impact of endothelial cells with and on the efficacy of first-line therapy(platinum-based or tyrosine kinase inhibitor drugs treatments)for advanced non-small-cell lung cancer.Methods:We analyzed 45 inpatients who met the inclusion criteria of diagnosis with inoperable non-small-cell lung cancer stages III and IV,in the People’s Hospital of Guangxi Zhuang Autonomous Region from January 2019 to January 2020.The flow cytometry technique was adopted to detect pretreatment levels of circulating endothelial cells in peripheral blood of patients with advanced non-small-cell lung cancer.The pretreatment peripheral blood was collected to analyze the relations of circulating endothelial cells with different clinical characteristics and efficacy.Results:The level of pretreatment circulating endothelial cells was significantly correlated with the efficacy of treatment(P<0.05)but irrelevant to the patient’s physical conditions,pathological type,tumor stage,and pretreatment serum carcinoembryonic antigen(P>0.05).The comparison between the groups of response(complete response+partial response)and nonresponse(stable disease+progressive disease)showed a significant difference in circulating endothelial cells count.Compared with low levels of circulating endothelial cells,a high level of circulating endothelial cells led to a poor efficacy(P<0.05).Conclusion:The level of pretreatment circulating endothelial cells significantly correlated with the efficiency of first-line therapy for non-small-cell lung cancer.Compared with low level of circulating endothelial cells,high level of circulating endothelial cells lead to poor efficacy.Therefore,circulating endothelial cell is indeed an effective indicator for predicting the efficacy of first-line therapy for advanced non-small-cell lung cancer.
基金Greece and the European Union(European Social Fund-ESF)through the Operational Programme“Human Resources Development,Education and Lifelong Learning”in the context of the project“Strengthening Human Resources Research Potential via Doctorate Research”(MIS-5000432),implemented by the State Scholarships Foundation(ΙΚΥ)the special account for research grants of the National and Kapodistrian University of Athens,Athens,Greece.
文摘BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium.They also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and neovascularization.Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities.However,the effects of exercise on EPCs in different stages of CHF remain under investigation.AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different severity.METHODS Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle ergometer.Venous blood was sampled before and after CPET.Five circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated cells.RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:2(1-2)vs post CPET:3(2-5)cells/106 enucleated cells,P<0.001],while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:42(19-73)vs post CPET:90(39-118)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:2(1-3)vs post CPET:6(3-9)cells/106 enucleated cells,P<0.001],CD34+/CD133+/VEGFR2[pre CPET:10(7-18)vs post CPET:14(10-19)cells/106 enucleated cells,P<0.01],CD34+/CD45-/CD133-[pre CPET:218(158-247)vs post CPET:311(254-569)cells/106 enucleated cells,P<0.001]and CD34+/CD45-/CD133-/VEGFR2[pre CPET:1(1-2)vs post CPET:4(2-6)cells/106 enucleated cells,P<0.001].A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak,ventilation/carbon dioxide output slope and EF as well(P<0.05).However,there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison(P>0.05).CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients,but this increase was not associated with syndrome severity.Further investigation,however,is needed.
基金by Science and Technology Development Fund Program of Higher Education of Tianjin,No.20120121。
文摘BACKGROUND Acute respiratory distress syndrome(ARDS)is injury of alveolar epithelial cells and capillary endothelial cells caused by various factors,including endogenous and exogenous lung factors,leading to diffuse pulmonary interstitial and alveolar edema,and acute respiratory failure.ARDS involves alveolar epithelial cells and pulmonary interstitial capillary endothelial cells.Circulating endothelial cells(CECs)are the only marker that directly reflects vascular endothelial injury in vivo.There have been few studies on the correlation between peripheral blood CECs and ARDS at home and abroad.The lungs are the organs with the highest capillary density and the most endothelial cells,thus,it is speculated that when ARDS occurs,CECs are stimulated and damaged,and released into the circulatory system.AIM To explore the correlation between CEC level and severity of ARDS in patients postoperatively.METHODS Blood samples were collected from all patients on day 2(d2)and day 5(d5)after surgery.The control group comprised 32 healthy volunteers.Number of CECs was measured by flow cytometry,and operation time was recorded.Changes in various indexes of patients were monitored,and diagnosis of ARDS was determined based on ARDS Berlin definition.We comprised d2 CECs in different groups,correlation between operation time and d2 CECs,ARDS of different severity by d2 CECs,and predictive value of d2 CECs for ARDS in postoperative patients.RESULTS The number of d2 CECs in the ARDS group was significantly higher than that in the healthy control group(P<0.001).The number of d2 CECs in the ARDS group was significantly higher than that in the non-ARDS group(P<0.001).The number of d2 CECs in the non-ARDS group was significantly higher than that in the healthy control group(P<0.001).Operation time was positively correlated with number of CECs on d2(rs=0.302,P=0.001).The number of d2 CECs in the deceased group was significantly higher than that in the improved group(P<0.001).There was no significant difference in number of d2 CECs between patients with mild and moderate ARDS.The number of d2 CECs in patients with severe ARDS was significantly higher than that in patients with mild and moderate ARDS(P=0.041,P=0.037).There was no significant difference in number of d5 and d2 CECs in the non-ARDS group after admission to intensive care.The number of d5 CECs was higher than the number of d2 CECs in the ARDS improved group(P<0.001).The number of d5 CECs was higher than the number of d2 CECs in the ARDS deceased group(P=0.002).If the number of CECs was>1351/mL,sensitivity and specificity of predicting ARDS were 80.8%and 78.1%,respectively.CONCLUSION Changes in number of CECs might predict occurrence and adverse outcome of ARDS after surgery,and higher numbers of CECs indicate worse prognosis of ARDS.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFC2704000)the National Natural Science Foundation of China(No.81971360).
文摘Background:Endometriosis(EM)is a complex benign gynecological disease,but it has malignant biological behavior and can invade any part of the body.Clinical manifestations include pelvic pain,dysmenorrhea,infertility,pelvic nodules,and masses.Our previous study successfully detected circulating endometrial cells(CECs)in the peripheral blood of patients with EM.The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method,to further accurately capture CECs,understand the characteristics of these cells,and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods:Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells(CVECs)was taken from EM patients(n=34)hospitalized in the Peking University People’s Hospital.We used the subtraction enrichment and immunostaining fluorescence in situ hybridization(SE-iFISH)method to exclude the interference of red blood cells,white blood cells,and CVECs,so as to accurately capture the CECs in the peripheral blood of patients with EM.Then we clarified the size and ploidy number of chromosome 8 of CECs,and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics.Results:The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH.Overall,34 eligible EM patients were enrolled.The results showed that the detection rates of CECs were 58.8%in EM patients and 16.7%in the control group.However,after classification according to clinical characteristics,more CECs could be detected in the peripheral blood of patients with rapidly progressive EM,with a detection rate of 94.4%(17/18).In total,63.5%(40/63)of these cells were small cells with diameters below 5μm,and 44.4%(28/63)were aneuploid cells.No significant association was found between the number of CECs and EM stage.Conclusion:The number and characteristics of CECs are related to the clinical course characteristics of patients with EM,such as pain and changes in lesion size,and may be used as biomarkers for personalized treatment and management of EM in the future.
文摘OBJECTIVE: To study the ehanges of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation anti pancreatic microcirculation in rats with acute edematous pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: PECAM-I expression on PMNs showed no significant difference between pancreatic microcirculation and peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated, but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1 expression had a significant difference between pancreatic microcirculation and peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1 expression on PMNs is in a converse way between pancreatic microcirculation and peripheral circulation in AEP.
文摘The number of the circulating angiogenic cells （CACs） and colony forming units （CFUs） derived from cultured circulating mononuclear cells （MNCs） represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction （ED） and vascular risk factors （VRFs） showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4weeks of treatment with tadalafil （20 mg every other day） or with a placebo. The tadalafil treatment improved erectile function （P = 0.0028）, but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 （P = 0.011） and tissue type plasminogen activator （P = 0.005） were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.
文摘Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually <3 cm red, fleshy, ulcerated skin lesions, that characteristically occur on sun-damaged skin, sometimes in immunocompromised or previously irradiated patients. These are part of a spectrum of more aggressive fibro-histiocytic neoplasms. In the older literature, these have been termed aggressive or metastatic AFX, but currently these have been reclassified as pleomorphic dermal sarcomas (PDS) and systemic undifferentiated pleomorphic sarcoma (UPS, formerly malignant fibrohistiocytic sarcoma, MFH). We present the case of a 64-year old woman who developed a deeply invasive PDS on the vertex of her scalp invading to the galea, with in-transit scalp metastases. Very little information is available about optimal treatment of metastatic PDS lesions. The patient was initially treated with 2 cycles of epirubicin/ifosfamide chemotherapy, resulting in life-threatening complications. A pretreatment peripheral blood sample was sent for CTC-derived colony assay. This sample grew 8 colonies from 10 ml blood. The tumor failed to respond to epirubicin and ifosfamide, and after several months of hospitalization, a second peripheral blood CTC-derived colony assay grew >376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to function as a potential prognostic marker.
文摘Background:The goal of this project was to analyze the relationship between cell morphology and proteases/proteases inhibitors(PIs)secretion profile in fuchs endothelial corneal dystrophy(FECD)corneal endothelial cells(CECs).Methods:Cell morphology was determined using a circularity index(4π×area/perimeter2)for each CECs population extracted from surgical FECD specimens(N=2)and healthy Eye bank corneas(N=3).CECs were cultured 28 days post-confluency.Supernatant was collected and analysed using Proteome Profiler Array detecting 35 proteases and 32 PIs(R&D Systems).Proteome signal was analyzed using Image Studio Lite and correlated with the population’s circularity index.Results:Calculation of circularity index reported different morphologies among FECD populations(0.59±0.18 and 0.64±0.17)and healthy populations(0.44±0.18,0.66±0.13 and 0.71±0.11).Proteome arrays revealed the presence of 10 proteases(ADAMTS1,Cathepsin A,B,D,and X/Z/P,DPPIV/CD26,MMP-2,3 and 12,uPA/Urokinase)and 10 PIs(Protease Nexin II,Cystatin B and C,EMMPRIN/CD147,Latexin,Lipocalin-1,Serpin E1,TFPI,TFPI-2,TIMP-1,2 and 4).Healthy and FECD specimens showed similar variation patterns according to morphology for secretion of ADAMTS1,MMP-3 and 12.However,opposing patterns between healthy and FECD populations were observed for Cathepsin B and D.Moreover,some proteins did not show variation according to phenotype in healthy CECs,but did in FECD CECs:Cathepsin A,Cystatin C,TFPI-2 and total TIMPs.For the other proteins,secretion did not vary according to morphology or no specific pattern was distinguishable.Conclusions:To conclude,our results suggest that cell phenotype is linked to the secretion of certain proteases/PIs in both groups.However,there seems to be differences in secretion of particular proteases and PIs between FECD and healthy specimens as morphology did not have a similar influence.These differences might initiate an imbalance between proteases and PIs explaining the irregular thickening of the Descemet membrane seen in FECD.
