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Objective To explore the changes of serum angiopoietin-like protein 4(ANGPTL4)and NOD-like receptor protein 3(NLRP3)levels after traumatic brain injury(TBI)and their diagnostic value for sec-ondary massive cerebral infarction.Methods A total of 100 TBI patients admitted to the hospital from Au-gust 2019 to August 2021 were enrolled as the TBI group,meantime,100 healthy people in the hospital were enrolled as the control group.The serum levels of ANGPTL4 and NLRP3 were detected by enzyme-linked im-munosorbent assay(ELISA).The clinical characteristics of TBI patients with and without secondary massive cerebral infarction were compared.Receiver operating characteristic(ROC)curve was applied to analyze the serum levels of ANGPTL4 and NLRP3 on their diagnostic value for TBI patients with secondary massive cere-bral infarction.Multivariate Logistic regression analysis was applied to analyze the factors affecting the occur-rence of secondary massive cerebral infarction in TBI patients.Results The serum ANGPTL4 level in TBI group was lower than that in the control group,and the serum NLRP3 level was higher than that in the con-trol group(P<0.05).There were obvious differences in proportion of brain hernia,proportion of subarach-noid hemorrhage,serum levels of ANGPTL4 and NLRP3 between patients with secondary massive cerebral infarction and patients without secondary massive cerebral infarction(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum ANGPTL4 and NLRP3 in diagnosing secondary massive cere-bral infarction in TBI patients was 0.792 and 0.812 respectively,with sensitivity of 77.80%and 83.30%re-spectively,and specificity of 86.60%and 64.60%respectively.The sensitivity,the specificity and AUC of the combined detection were 83.30%,82.90%and 0.867 respectively.Multivariate Logistic regression analysis showed that serum NLRP3 level was a risk factor for TBI patients with secondary massive cerebral infarction(P<0.05).After treatment,it was found that serum ANGPTL4 level increased and NLRP3 level decreased in TBI patients(P<0.05).Conclusion The serum level of ANGPTL4 in TBI patients decreases,while the level of NLRP3 increases,and the level of ANGPTL4 in the serum of patients with secondary massive cerebral in-farction decreases and the level of NLRP3 increases,both of them are of great significance in the diagnosis of secondary massive cerebral infarction in TBI patients.
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Angiopoietin-like protein 8(ANGPTL8)secreted by liver and adipose tissue,is a glycoprotein exerting paramount effects on facilitation of vascular remodeling and regulation of inflammatory response;ANGPTL8 is in-volved in the initiation and progression of cardiovascular diseases including coronary artery disease,hypertension,aortic aneurysm and pathological cardiac hypertrophy,and holds promise for being a new target for the prevention and treatment of cardiovascular diseases.
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Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores<Gensini score≤60 scores)and severe stenosis group(Gensini score>60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.
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ObjectiveTo investigate the correlation of serum angiopoietin-1 （Ang-1）， angiopoietin-2 （Ang-2）， and Ang-1/Ang-2 ratio with HBA DNA and alanine aminotransferase （ALT） in patients with chronic hepatitis B （CHB） or liver cirrhosis. MethodsClinical data and serum specimens were collected from 99 patients with CHB and 59 patients with liver cirrhosis who were admitted to Beijing YouAn Hospital， Capital Medical University， from March 2018 to October 2019， and 46 individuals who underwent physical examination were enrolled as control group. PCR was used to measure serum HBV DNA level， and ELISA was used to measure the serum levels of Ang-1 and Ang-2. The serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio were compared between groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Bonferroni method was used for further comparison between two groups； the Spearman correlation analysis was used to investigate the correlation of Ang-1， Ang-2， and Ang-1/Ang-2 ratio with HBV DNA and ALT. ResultsCompared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in the level of Ang-1 （479.0 pg/mL and 208.4 pg/mL vs 671.0 pg/mL， both P<0.05）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in the level of Ang-1 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant increase in the level of Ang-2 （286.1 pg/mL and 438.4 pg/mL vs 198.0 pg/mL， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant increase in the level of Ang-2 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （1.6 and 0.5 vs 3.4， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （P<0.001）. The Spearman correlation analysis showed that in the CHB group， Ang-1 was negatively correlated with HBV DNA and ALT （r=-0.400 and -0.394， both P˂0.001）， Ang-2 was positively correlated with HBV DNA and ALT （r=0.365 and 0.351， both P<0.001）， and Ang-1/Ang-2 ratio was negatively correlated with HBV DNA and ALT （r=-0.463 and -0.473， both P<0.001）； in the liver cirrhosis group， Ang-1， Ang-2， and Ang-1/Ang-2 ratio had no correlation with HBV DNA or ALT （all P>0.05）. ConclusionThere are significant changes in the serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio in patients with CHB or liver cirrhosis， and Ang-1， Ang-2， and Ang-1/Ang-2 ratio reflects the degree of liver injury in patients with CHB to a certain extent.
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Objective To investigate the correlation between angiopoietin-2(Ang-2)and intestinal fatty acid binding protein(I-FABP)levels and the prognosis of acute myocardial infarction(AMI)with cardiac shock(CS).Methods A total of 198 patients with AMI admitted to Huzhou Central Hospital from July 2017 to July 2019 were selected as study objects,and were divided into CS group(n=93)and non-CS group(n=105)according to whether CS occurred during the hospital period,and 65 normal volunteers admitted for physical examination during the same period were included in control group.Patients in CS group were divided into survival group(n=50)and death group(n=43)according to their survival at 28 days.Serum Ang-2 and I-FABP levels of all subjects were detected,and Cox regression analysis was used to analyze the factors affecting the poor prognosis of AMI with CS.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of Ang-2 and I-FABP in AMI with CS.Results Serum Ang-2 and I-FABP levels in CS group were significantly higher than those in non-CS group and control group(P<0.05),and serum Ang-2 and I-FABP levels in non-CS group were significantly higher than those in control group(P<0.05).Serum Ang-2,I-FABP levels and proportion of diabetes in death group were significantly higher than those in survival group(P<0.05).Cox regression analysis showed that diabetes,Ang-2 and I-FABP levels were independent factors affecting the prognosis of AMI with CS(P<0.05).ROC curve showed that the area under the curve of Ang-2 and I-FABP combined to predict the prognosis of AMI with CS was 0.819,sensitivity was 81.4%,specificity was 80.0%.Conclusion Serum Ang-2 and I-FABP levels were elevated in patients with AMI with CS,which were potential biological indicators to predict the prognosis of patients.
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ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg-1·d-1）， and indometacin group （10 mg·kg-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.
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ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.
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Abstract Background Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. Objective This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. Methods RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. Results ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. Study limitations The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. Conclusions ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS.
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@#Angiopoietin-like 4(ANGPTL4)is one of the angiopoietin family members and plays a regulatory role in lipid metabolism,glucose homeostasis,inflammatory signal transduction,angiogenesis and vascular permeability.Inflammatory reaction in tumor microenvironment regulates tumor progression,and tumor angiogenesis plays a vital role in tumor growth and metastasis,so ANGPTL4 is closely related to tumor occurrence and development.Many studies have shown that ANGPTL4 plays an important regulatory role in tumor growth,anoikis resistance,tumor angiogenesis and tumor metastasis.This paper reviews the role of ANGPTL4 in tumor progression.
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Objective @# To investigate the effects of angiopoietin 4 (ANGPT4) on the odontogenic differentiation of human dental pulp stem cells. @* Methods @#This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Human premolars were fixed, decalcified, dehydrated, embedded, and sectioned. Immunofluorescence staining was used to observe the expression and localization of ANGPT4. Human dental pulp stem cells (hDPSCs) were isolated and cultured in vitro. The growth state and morphology of hDPSCs were observed under an inverted phase contrast microscope. The expression of cell surface-related molecular markers was detected by flow cytometry. Alkaline phosphatase and alizarin red S staining were used to detect the odontogenic differentiation potential of hDPSCs. Oil-red O staining was used to detect the adipogenic differentiation potential of hDPSCs. RNA was extracted from hDPSCs at different time points after odontogenic induction, and RT-qPCR was used to analyze the mRNA expression of ANGPT4 and odontogenic-related genes during the odontogenic differentiation of hDPSCs in vitro. siRNA gene silencing technology was used to silence the expression of ANGPT4 in hDPSCs, and the silencing efficiency was detected by RT-qPCR and Western Blot. After silencing ANGPT4 in hDPSCs for 24 h, odontogenic induction was performed. Alkaline phosphatase and alizarin red S staining were performed on the 7th and 14th of induction to detect the odontogenic differentiation ability of hDPSCs after silencing ANGPT4@*Results @# Immunofluorescence staining of human premolars showed that ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone. hDPSCs were in good condition after 14 days of isolation and culture. Under the microscope, multiple cell colonies were observed, and the cell morphology was uniform and long spindle-shaped. The results of flow cytometry showed that hDPSCs expressed mesenchymal stem cell markers CD105 (90.42%) and CD90 (97.15%), but did not express hematopoietic cell markers CD45 (0.01%) and CD34 (0.08%). After odontogenic and adipogenic induction of hDPSCs, alkaline phosphatase staining, alizarin red S staining and oil red O staining were positive. The results of RT-qPCR after the odontogenic induction of hDPSCs showed that ANGPT4 was highly expressed on the 5th, 7th, 11th and 14th days of differentiation of hDPSCs (P<0.05), with the highest expression level on the 5th day. After hDPSCs were transfected with si-ANGPT4, the expression of ANGPT4 mRNA and protein was significantly down-regulated (P<0.05). The results of alkaline phosphatase staining showed that ALP staining intensity and area in the si-ANGPT4 group were significantly lower than those in the negative control. Alizarin red S staining showed that the formation of calcium nodules in the si-ANGPT4 group was significantly lower than that in the negative control.@* Conclusion@#ANGPT4 was expressed in odontoblasts and sub-odontoblastic cell-rich zone of human premolars. ANGPT4 may be a factor to promote the odontogenic differentiation of hDPSCs.
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Objective To investigate the correlation of serum levels of Krüppel-like transcription factor 2(KLF2)and angiopoietin-1(Ang1)with the severity and prognosis of neonatal respiratory distress syndrome(NRDS).Methods A total of 416 children with NRDS who were treated in this hospital from January 2019 to December 2022 were selected as the NRDS group.According to the results of chest imaging examination,the NRDS group was divided into mild group(145 cases),moderate group(174 cases)and severe group(97 ca-ses).According to NRDS outcome the children were divided into the good prognosis group 322 cases and bad prognosis group 94 cases,another 150 healthy premature infants were selected as the control group in the hos-pital.Serum KLF2,Ang1 levels were measured by enzyme-linked immunosorbent assay(ELISA).Pearson correlation was used to analyze the correlation between serum KLF2,Ang1 levels and neonatal acute physiolo-gy score perinatal supplement Ⅱ(SNAPPE-Ⅱ),1 min Apgar score in neonates with NRDS.The receiver op-erating characteristic(ROC)curve was used to evaluate the value of serum KLF2,Ang1 levels in predicting the prognosis of children with NRDS.Results Compared with the control group,the NRDS group had signifi-cantly lower birth weight and serum KLF2,Ang1 levels(P<0.05).In the children with NRDS,the serum of KLF2,Ang1 levels and 1 min Apgar score gradually decreased with the increase in the severity of the disease(P<0.05).Compared with the good prognosis group,the children with NRDS in the poor prognosis group had significant decreased in the serum KLF2 and Ang1 levels and a significant increased in the SNAPPE-Ⅱscore(P<0.05).In children with NRDS,the serum levels of KLF2 and Ang1 were negatively correlated with SNAPPE-Ⅱ score and positively correlated with 1 min Apgar score(P<0.05).The area under the curve(AUC)of serum KLF2 and Ang1 levels in predicting the poor prognosis of NRDS children were 0.931 and 0.909,respectively.The AUC of the combination of KLF2 and Ang1 in predicting the poor prognosis of NRDS children was 0.949,which was higher than that of KLF2 or Ang1 alone,with a sensitivity of 96.81%.Conclu-sion Serum KLF2,Ang1 levels in children with NRDS are reduced,the two level with NRDS children with severe degree aggravating gradually decreas,and both have important value in predicting the prognosis of chil-dren with NRDS.
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Objective The combined detection of serum angiopoietin-like protein 8(ANGPTL8)and Vascular cell adhesion molecule-1(VCAM-1)levels was analyzed for the predictive value of cerebral vasospasm(CVS)after intracranial aneurysm embolization.Methods A total of 196 patients who underwent intracranial aneurysm embolization in our hospital from March 2019-March 2022 were selected as the study subjects,99 patients with CVS were in the CVS group,and 97 patients without CVS were in the non CVS group.Serum ANGPTL8 and VCAM-1 levels were detected by ELISA;the correlation between serum ANGPTL8 and VCAM-1 levels was analyzed by Pearson method,Logistic regression was used to analyze the influencing factors of CVS in patients undergoing intracranial aneurysm embolization;ROC curve was used to analyze the serum levels of ANGPTL8 and VCAM-1 to predict the cutoff value of CVS in patients undergoing intracranial aneurysm embolization;four grid table method was used to analyze the predictive value of ANGPTL8,VCAM-1 and their combination on the occurrence of CVS in patients undergoing intracranial aneurysm embolization.Results The differences between CVS and non-CVS groups were statistically significant in hypertension,Hunt-Hess grade,and Glasgow coma(GCS)scores(P＜0.05).The serum ANGPTL8 and VCAM-1 levels in the CVS group were significantly higher than those in the non-CVS group(P＜0.05).There was a positive correlation between serum ANGPTL8 and VCAM-1(r=0.468,P＜0.05).Multivariate analysis showed that high level of ANGPTL8(OR=3.652,95％CI:1.434-9.302),high level of VCAM-1(OR=2.619,95％CI:1.212-5.658),Hunt Hess grade Ⅲ-Ⅳ(OR=1.927,95％CI:1.104-3.362),GCS score of 3-8(OR=2.813,95％CI:1.257-6.295)were independent risk factors for CVS in patients undergoing intracranial aneurysm embolization.The AUC of serum ANGPTL8 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.844,and the cut-off value was 189.233 U/L;the AUC of serum VCAM-1 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.795,and the cutoff value was 17.984 mg/L.The accuracy,sensitivity and specificity of the combined prediction for CVS were 89.81％,93.94％and 85.57％,respectively,which were obviously higher than those of the single prediction.Conclusion The serum levels of ANGPTL8 and VCAM-1 in CVS group are obviously higher than those in non CVS group.The combination of the two has a high predictive value for CVS after intracranial aneurysm embolization.
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Objective To investigate the changes in serum levels of angiopoietin-like protein 4(ANGPTL4)and ubiquitin carboxyl terminal hydrolase-1(UCH-L1),and CHA2DS2-VASc score in patients with non-valvular atrial fibrillation(NVAF)and acute cerebral infarction(ACI),and their diagnostic value.Methods A total of 162 NVAF patients treated in our hospital from Janu-ary 2021 to January 2023 were enrolled and divided into a combined group(45 cases)and a non-combined group(117 cases)according to having ACI or not.General clinical information,CHA2DS2-VASc scores,and serum levels of ANGPTL4 and UCH-L1 were collected and detected.Spearman correlation analysis was applied to evaluate the correlation of ANGPTL4,UCH-L1 and CHA2DS2-VASc score.Multivariate logistic regression analysis was performed to identify the in-fluencing factors of NVAF combined with ACI.ROC curve was plotted to evaluate the diagnostic value of serum ANGPTL4,UCH-L1,and CHA2DS2-VASc score for NVAF combined with ACI.Results The ANGPTL4 level was significantly lower,and the UCH-L1 level and CHA2DS2-VASc score were obviously higher in the combined group than the non-combined group(P＜0.05).In the patients with NVAF combined with ACI,serum ANGPTL4(r=-0.548,P＜0.05)and UCH-L1(r=0.400,P＜0.05)levels were negatively and positively correlated with CHA2DS2-VASc score,respectively.ANGPTL4,UCH-L1 and CHA2DS2-VASc were the risk fac-tors for ACI in NVAF patients(P＜0.05,P＜0.01).The AUC value of combined serum ANGPTL4 and UCH-L1 levels and CHA2DS2-VASc score for diagnosing NVAF complicated with ACI was 0.926(95％CI:0.874-0.961).Conclusion Combined detection of serum AUCH-L1 and NGPTL4 levels and CHA2DS2-VASc score can significantly improve the diagnostic value of NVAF patients with ACI.
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Objective To investigate the correlation between the expression of angiopoietin-2(Ang-2),lymphatic vessel endo-thelial hyaluronan receptor-1(LYVE-1)and the biological characteristics of cutaneous squamous cell carcinoma.Methods A total of 44 patients with primary cSCC admitted to the Affiliated Hospital of Jiangsu University from September 2013 and February 2021 were in-cluded.The expression levels of Ang-2 and LYVE-1 in their cSCC specimens was detected by immunohistochemistry(IHC).The ex-pression level of LYVE-1 was expressed by the microlymphatic vessel density(MLVD).Results The high expression rate of Ang-2 in cSCC group without lymph node metastasis was 44％(15/34),which was significantly lower than that in CSCC group(90％,9/10),and the difference was statistically significant(P＜0.05).The high expression rate of Ang-2 in the highly differentiated cSCC group was 35％(9/26),which was significantly lower than that in the medium and poorly differentiated CSCC group(83％,15/18),and the differ-ence was statistically significant(P＜0.05).The expression of LYVE-1 in cSCC group without lymph node metastasis was 8.49±4.26,which was significantly lower than that in cSCC group(13.48±5.91),and the difference was statistically significant(P＜0.05).The expression of LYVE-1 in highly differentiated cSCC group was 6.39±2.09,which was significantly lower than that in medium and poor-ly differentiated cSCC group(14.28±4.42),and the difference was statistically significant(P＜0.05).The expression of Ang-2 and LYVE-1 was not related to gender,age and tumor size(P＞0.05).The expression level of Ang-2 was positively correlated with LYVE-1(r=0.598,P＜0.01).Conclusion Ang-2 and LYVE-1 are involved in promoting the occurrence,development and lymph node metastasis of cSCC.
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Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.
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Angiopoietin-like protein 4 (ANGPTL4) is involved in the regulation of glucose and lipid metabolism and angiogenesis, and is closely related to tumorigenesis, development, invasion and metastasis. The abnormal expression of ANGPTL4 gene can promote or inhibit the growth and proliferation of tumor cells and play a tumor-promoting or anti-tumor role in the occurrence and development of tumors. To explore the role of ANGPTL4 gene in the occurrence and development of different tumors can provide reference for evaluating the diagnosis, prognosis and curative effect of tumors.
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Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.
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Objective:To explore the relationship between the expression of angiopoietin 1 (ANGPT1) and Smadhomolog 9 (Smad9) genes in cancer tissues and tumor metastasis, invasion behavior and prognosis in patients with lung adenocarcinoma.Methods:Sixty patients with lung adenocarcinoma in Chengwu Hospital Affiliated to Shandong First Medical University from October 2018 to December 2019 were selected as the research objects. The expressions of ANGPT1 and Smad9 mRNA in cancer tissues and adjacent tissues were compared, as well as the expressions of ANGPT1 and Smad9 mRNA in cancer tissues of patients with different tumor metastasis and invasion behaviors. The relationship between ANGPT1 and Smad9 mRNA expression and tumor metastasis and invasion behavior of lung adenocarcinoma were analyzed, and the 1-year survival rate of patients with lung adenocarcinoma was calculated. The 1-year survival rate of patients with different ANGPT1 and SMAD9 mRNA expression levels were compared.Results:The relative expression of ANGPT1 mRNA and Smad9 mRNA in cancer tissues were lower than those in adjacent tissues: 2.45 ± 0.26 vs. 11.18 ± 0.93, 4.23 ± 0.31 vs. 7.58 ± 0.65, the differences were statistically significant ( P<0.05). There were significant differences in the relative gene expression of ANGPT1 and Smad9 mRNA in different clinical stages, tumor diameter, degree of differentiation, lymph node metastasis and pleural invasion ( P<0.05). Spearman correlation analysis showed that the expression of ANGPT1 and Smad9 mRNA were negatively correlated with clinical stage, tumor diameter, lymph node metastasis and pleural invasion ( r = - 0.517, - 0.539, - 0.606, - 0.679, P<0.05), and positively correlated with the degree of differentiation ( r = 0.628, P<0.05). The 1-year survival rate of 58 patients was 72.41%. Kaplan-Meier curve analysis showed that the 1-year survival rate of patients with low expression of ANGPT1 and Smad9 mRNA in cancer tissues were were lower than those in patients with high expression ( P<0.05). Conclusions:Down-regulation of ANGPT1 and Smad9 genes in cancer tissues will accelerate the metastasis and invasion behavior of lung adenocarcinoma. Up-regulating the expression of both genes can be a potential way to improve survival.
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Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.
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Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.