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SUMMARY OBJECTIVE: Coronary artery disease is the leading cause of death worldwide. Vascular endothelial growth factor is known to induce endothelial cell migration and proliferation, increase vascular permeability, and modulate thrombogenicity. The aim of this study is to investigate the relationship between the VEGF insertion/deletion (I/D) variant (rs35569394) and coronary artery disease susceptibility in the Turkish population. METHODS: A total of 206 subjects, including 106 coronary artery disease patients and 100 controls, were included in this study. The VEGF I/D variant was genotyped using the polymerase chain reaction method. RESULTS: The frequency of the I/I, I/D, and D/D genotypes was 35.84 versus 37%, 33.97 versus 36%, and 30.19 versus 27% in patients and the control group, respectively. VEGF I/D genotype and allele distribution were not statistically significant between coronary artery disease patients and controls (p>0.05). There was no significant difference between VEGF I/D genotype distribution and patient characteristics including age, gender, disease duration, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, history of hypertension, history of diabetes mellitus, and smoking (p>0.05). CONCLUSION: This study suggests that the VEGF I/D variant is not a predisposing factor to coronary artery disease disease in a Turkish sample.
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Objective:To discuss the effect of ligustilide on the cardiac function and angiogenesis in the rats with heart failure,and to clarify its regulatory effect on protein kinase D1(PKD1)/hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:The SD rats were randomly divided into sham operation group,model group,ligustilide group,PKD1/HIF-1α/VEGF signaling pathway inhibitor CID755673(CID)group,and ligustilide+CID group.The heart failure rat model was established by ligation of the left anterior descending coronary artery.The rats in ligustilide group were injected intravenously with 20 mg·kg-1 ligustilide,the rats in CID group were injected intraperitoneally with 50 mg·kg-1 CID,and the rats in ligustilide+CID group were injected intraperitoneally with 50 mg·kg-1 CID followed by intravenous injection of 20 mg·kg-1 ligustilide,once per day for 4 consecutive weeks.The cardiac function indexes of the rats in various groups were detected by echocardiography;the percentages of myocardial infarction areas of the rats in various groups were detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathomorphology of myocardium tissue of the rats in various groups was observed by HE staining;the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in ischemic area of myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.Results:Compared with sham operation group,the rats in model group and CID group had altered myocardial cell morphology,increased intercellular gaps,disorganized arrangement,visible muscle fiber breaks and inflammatory cell infiltration;the rats in ligustilide group and ligustilide+CID group had relatively orderly myocardial fiber arrangement,fewer myocardial fiber breaks and decreased number of inflammatory cells.Compared with sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rats in model group were decreased(P<0.05),the left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD)were increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05).Compared with model group,the LVEF and LVFS of the rats in ligustilide group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05);compared with model group,the LVEF and LVFS of the rats in CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with ligustilide group,the LVEF and LVFS of the rats in ligustilide+CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with CID group,the LVEF and LVFS of the rats in ligustilide+CID group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05).Conclusion:Ligustilide can promote the angiogenesis,reduce the myocardium infarction area,and improve the cardiac function in the rats with heart failure;it works through activation of the PKD1/HIF-1α/VEGF pathway.
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Objective:To explore the effects of Tongdu Tiaoshen acupuncture on vascular endothelial function and inflammatory factors in patients with mild cognitive impairment (MCI) after ischemic stroke (IS).Methods:A retrospective analysis was performed on the clinical data of 71 patients with MCI after IS in the hospital between January 2020 and September 2022. According to different treatment methods, they were divided into Tongdu Tiaoshen acupuncture group ( n=31, Tongdu Tiaoshen acupuncture + oral nimodipine tables) and routine body-acupuncture group ( n=40, routine body-acupuncture group + oral nimodipine tables). Both groups were treated for 2 courses (14 d/course). Before and after treatment, levels of serum NO and endothelin-1 (ET-1) were detected by radioimmunoassay, and levels of serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), plasma homocysteine (Hcy) and IL-6 were detected by ELISA. The cognitive function of patients was evaluated and intelligence level by Montreal Cognitive Assessment Scale (MoCA), Mini-Mental State Examination(MMSE) and the clinical curative effect was also evaluated. Results:The total response rates in Tongdu Tiaoshen acupuncture group and routine body-acupuncture group were 90.32% (28/31) and 70.00% (28/40), and the difference between the two groups was statistically significant ( χ2=4.33, P=0.037). After treatment, levels of plasma Hcy and IL-6 in Tongdu Tiaoshen acupuncture group were lower than those in the routine body-acupuncture group ( t=2.57, 9.36, P<0.05 or P<0.01). After treatment, levels of serum bFGF, VEGF and NO in Tongdu Tiaoshen acupuncture group were significantly higher than those in the routine body-acupuncture group ( t=10.03, 9.29, 8.17, P<0.01), while ET-1 level was significantly lower than that of the routine body-acupuncture group ( t=2.41, P=0.019). After treatment, MoCA score [(28.24±4.45) vs. (25.32±4.34), t=2.78], MMSE score [(28.73±1.44) vs. (28.02±1.22), t=2.25] in Tongdu Tiaoshen acupuncture group were higher than those in the routine body-acupuncture group ( P<0.01). Conclusion:Tongdu Tiaoshen acupuncture is beneficial to improve vascular endothelial function, reduce levels of inflammatory factors, promote the recovery of cognitive function and improve curative effect in patients with MCI after IS.
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Objective To investigate the clinical efficacy of Yiqi Huayu Decoction(mainly composed of Astragali Radix,Dioscoreae Rhizoma,Poria,fried Euryales Semen,Ecliptae Herba,Rosae Laevigatae Fructus,charred Crataegi Fructus,Ligustri Lucidi Fructus,Salviae Miltiorrhizae Radix et Rhizoma,and Leonuri Herba)combined with Calcium Dobesilate in the treatment of diabetic nephropathy(DN)with qi deficiency and blood stasis syndrome,and to observe the effect of the therapy on vascular endothelial growth factor(VEGF)and insulin-like growth factor 1(IGF-1).Methods Ninety patients with DN of qi deficiency and blood stasis type were randomly divided into an observation group and a control group,with 45 patients in each group.All patients received basic hypoglycemic therapy and treatment for controlling blood pressure and regulating lipid metabolism disorders.Moreover,the patients in the control group were given Calcium Dobesilate orally,and the patients in the observation group were given Yiqi Huayu Decoction combined with Calcium Dobesilate.The course of treatment lasted for 3 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters and serum VEGF and IGF-1 levels in the two groups of patients were observed before and after the treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 3 months of treatment,the total effective rate of the observation group was 91.11%(41/45),and that of the control group was 75.56%(34/45).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After one month and 3 months of treatment,the TCM syndrome scores of both groups were significantly lower than those before treatment(P＜0.05),and the scores after 3 months of treatment in the two groups were significantly lower than those after one month of treatment(P＜0.05).The intergroup comparison showed that the reduction of TCM syndrome scores of the observation group was significantly superior to that of the control group after one month and 3 months of treatment(P＜0.01).(3)After treatment,the levels of renal function parameters such as serum creatinine(Scr),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the observation group's effect on the improvement of all renal function parameters was significantly superior to that of the control group(P＜0.01).(4)After treatment,the serum VEGF and IGF-1 levels in the two groups of patients were significantly lower than those before treatment(P＜0.05),and the observation group's effect on the decrease of serum VEGF and IGF-1 levels was significantly superior to that of the control group(P＜0.01).(5)In the course of treatment,no significant adverse reactions occurred in the two groups of patients,with a high degree of safety.Conclusion Yiqi Huayu Decoction combined with Calcium Dobesilate exerts certain therapeutic effect in treating DN patients with qi deficiency and blood stasis syndrome.The combined therapy can effectively down-regulate the serum levels of VEGF and IGF-1,significantly improve the renal function,and alleviate the clinical symptoms of the patients,with a high degree of safety.
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Objective To observe the clinical efficacy of Yangxue Sanhan Tongmai Prescription(derived from the modification of Danggui Sini plus Wuzhuyu Shengjiang Decoction,i.e.,Danggui Sini Decoction with Euodiae Fructus and Zingiberis Rhizoma Recens added)for the treatment of endometriosis(EMS)of blood deficiency and cold coagulation type.Methods A total of 120 cases of EMS with blood deficiency and cold coagulation syndrome were randomly divided into the study group and the control group,with 60 cases in each group.The study group was treated with Yangxue Sanhan Tongmai Prescription,and the control group was treated with Shaofu Zhuyu Granules.Both groups were treated for a period of 3 months,and were followed up for one year after the completion of the treatment.The two groups were observed in the changes of the visual analogue scale(VAS)scores of menstrual abdominal pain,the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness,the size of ovarian endometriosis cysts,and the serum levels of carbohydrate antigen 125(CA125),vascular endothelial growth factor(VEGF),soluble intercellular adhesion molecule 1(SICAM-1),matrix metalloproteinase 9(MMP-9)and tissue inhibitor of metalloproteinase 2(TIMP-2).After treatment,the clinical efficacy and safety,recurrence and pregnancy in the two groups were evaluated.Results(1)In the course of the trial,3 cases fell off in the study group and 5 cases fell off in the control group,and a total of 112 patients were eventually included in the statistical analysis,including 57 cases in the study group and 55 cases in the control group.(2)After 3 months of treatment,the total effective rate in the study group was 92.98%(53/57)and that in the control group was 85.45%(47/55),and the intergroup comparison showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.05).(3)After treatment,VAS scores of menstrual abdominal pain and the grading scores of dysmenorrhea,non-menstrual pelvic pain,pain during sexual intercourse,pelvic pressure pain and sacral ligament tenderness in the two groups were significantly reduced compared with those before treatment(P＜0.05),and the reduction in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the ovarian endometriosis cysts of the two groups were slightly reduced,but the intragroup pre-and post-treatment differences and the intergroup post-treatment differences were not statistically significant(P＞0.05).(5)After treatment,the levels of serum CA125,VEGF,SICAM-1 and MMP-9 were decreased and the serum TIMP-2 level was increased in both groups compared with those before treatment(P＜0.05).And the decrease of serum CA125,VEGF,SICAM-1 and MMP-9 as well as the increase of serum TIMP-2 in the study group were significantly superior to those in the control group(P＜0.05).(6)The results of one-year follow-up showed that the recurrence rate of the study group was 30.19%(16/53),which was significantly lower than that of the control group(68.09%,32/47),and the difference was statistically significant between the two groups(P＜0.05).In the study group,there were 21 patients having the fertility desire,and then 14 cases of them were pregnant after treatment,with a pregnancy rate of 66.67%(14/21);in the control group,there were 20 cases having fertility desire,and then 4 cases of them were pregnant after treatment,with a pregnancy rate of 20.00%(4/20).The intergroup comparison showed that the pregnancy rate of the study group was significantly higher than that of the control group,and the difference was statistically significant(P＜0.05).(7)During the treatment period,there were no obvious adverse reactions in the two groups,and there were no abnormal changes in the safety indexes of blood,urine,and stool routine test,electrocardiogram,and liver and kidney function.Conclusion Yangxue Sanhan Tongmai Prescription exerts certain effect in treating patients with endometriosis of blood deficiency and cold coagulation type,which can significantly alleviate various pain symptoms,improve pregnancy outcomes,and effectively regulate the levels of serum CA125,VEGF,SICAM-1,MMP-9 and TIMP-2 of the patients.
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Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P＜0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P＜0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P＜0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P＞0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P＞0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.
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Objective To investigate the impacts of cinobufotalin combined with docetaxel+cisplatin chemotherapy on the disease control and the level of vascular endothelial growth factor(VEGF)in serum of patients with non-small cell lung cancer.Methods Totally 70 patients with non-small cell lung cancer admitted to Zhejiang Veteran Hospital from March 2019 to March 2022 were included.They were randomly divided into combination group(cinobufotalin combined with docetaxel+cisplatin,n= 35)and control group(docetaxel+cisplatin chemotherapy alone,n=35).The disease control rates of two groups,serum VEGF level,carcinoembryonic antigen(CEA),cy-tokeratin 19(CK19)and carbohydrate antigen 125(CA125)were measured using ELISA;life quality of patients was evaluated with the KPS score;The adverse events between two groups were compared.Results The disease control rate in the combination group(33/35,94.29％)was higher than that that of control group(25/35,71.43％,)(P＜0.05).After treatment,the level of VEGF in both groups of patients decreased,and the KPS score increased(P＜0.05)especially in the combination group(P＜0.05).After treatment,the level of serum CEA,CA125,and CK19 of control group and combination group were obviously lower than those before treatment(P＜0.05),while those in the combination group were even lower(P＜0.05).The incidence of adverse events in the combination group(5/35,14.29％)was lower than that in the control group(13/35,37.14％)(P＜0.05).Conclusions Cinobufotalin combined with docetaxel+cisplatin chemotherapy as a potential new chemotherapy significantly reduces the level of VEGF and tumor biomarkers in serum factor,improves the life quality of patients.The combined therapy is proved tobe safe.
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Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.
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Oral squamous cell carcinoma(OSCC),the most common type of head and neck tumor,is characterized by insidious onset,susceptibility to metastasis,short 5-year survival,and high mortality rate.Currently,various treatment modalities exist for OSCC;however,they inevitably give rise to issues related to non-specific cell death.Therefore,there is an urgent need to explore alternative therapeutic approaches for OSCC.This article provides a comprehensive overview of the recent advance-ments in OSCC treatment,aiming to offer new avenues for future therapeutic strategies.
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Objective To study the effect of geniposide(Gen)on the proliferation,migration and angiogenesis of human retinal vascular endothelial cells(hRVECs)induced by high glucose and explore its mechanism.Methods The hRVECs were intervened with different concentrations(0,1,5,10,20,40 and 80 mg·L-1)of Gen for 24 h,and Cell Counting Kit-8(CCK-8)was used to detect the effect of Gen on the proliferation activity of hRVECs.The hRVECs were di-vided into the control group,high glucose(25 mmol·L-1)group,low,middle and high Gen concentration(5,10 and 20 mg·L-1)groups,bevacizumab(BEV,250 μg·L-1)group and high Gen concentration+BEV(250 pg·L-1)group.Cell proliferation activity was detected by CCK-8.The cell migration ability was detected by scratch test.The tube formation ability of cells was detected by the in vitro tube formation assay.The protein expression levels of vascular endothelial growth factor-A(VEGF-A),soluble VEGF receptor-1(sFlt-1),matrix metalloproteinase 2(MMP-2)and matrix metallo-proteinase 9(MMP-9)in cells were detected by Western blot.Results Compared with 0 mg·L-1 Gen,there was no sta-tistically significant difference in the effect of Gen with concentrations of 1,5,10,20,40 and 80 mg·L-1 on the prolifera-tion activity of hRVECs(all P＞0.05).Compared with the control group,the proliferation activity and migration ability of hRVECs in the high glucose group were significantly enhanced(both P＜0.05),the cell circular structure increased,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly increased(all P＜0.05),and the protein expression level of sFlt-1 significantly decreased(P＜0.05).Compared with the high glucose group,the proliferative activity and mi-gration ability of cells in all Gen concentration groups and BEV group significantly decreased(all P＜0.05),the circular structure of cells was reduced,the protein expression levels of VEGF-A,MMP-2 and MMP-9 significantly decreased(all P＜0.05),and the protein expression level of sFlt-1 significantly increased(P＜0.05).Compared with the high Gen concentra-tion group,the high Gen concentration+BEV group showed a significant decrease in cell proliferation activity(P＜0.05),a decrease in cell circular structure,a significant decrease in VEGF-A,MMP-2 and MMP-9 protein expression levels(all P＜0.05),and a significant increase in sFlt-1 protein expression level(P＜0.05).Conclusion Gen can inhibit the high glucose-induced proliferation,migration and angiogenesis of hRVECs,and its mechanism may be related to the regulation of VEGF/sFlt-1 axis balance.
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Objective To investigate the efficacy and safety of subretinal fluid extraction combined with intravitreal conbercept and gas injection in treating polypoidal choroidal vasculopathy(PCV)complicated with serous retinal pigment epithelium detachment(sPED).Methods From July 2019 to February 2021,13 patients(13 eyes)with PCV complicated with sPED who were treated with subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the Weifang Eye Hospital were selected.All affected eyes received at least 3 times(once a month)of intravitreal anti-vas-cular endothelial growth factor(VEGF)(ranibizumab)injections before the surgery,and the treatment was ineffective.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),macular foveal PED height and width before and 1 week,1 month,3 months and 6 months after the operation were observed,and the intraoperative and postop-erative complications were recorded.Results The BCVA of the affected eyes 1 week after operation was better than that before operation,and the difference was statistically significant(Z=-3.237,P=0.001).The CRT of the affected eyes at 1 week,1 month,3 months and 6 months after the operation were thinner than that before the operation,and the differ-ence was statistically significant(Z=-3.180,-3.180,-3.110 and-3.180,P=0.001,0.001,0.002 and 0.001).The height and width of PED at 1 week,1 month,3 months and 6 months after the operation were lower than those before the operation,and the differences were statistically significant(all P＜0.05).Thirteen eyes received an average of(4.15±1.40)intravitreal injections(ranibizumab)before the surgery,and the treatment duration was(5.92±3.95)months(equivalent to one injection every 6 weeks).During the 6-month follow-up,13 eyes received an average of(2.31±1.97)intravitreal injections(conbercept)(equivalent to once every 10 weeks).Partial correlation analysis showed a weak positive correla-tion between the increase in BCVA and the decrease in CRT 6 months after operation(r=0.416,P=0.203).There was no significant correlation between the increase in BCVA and the changes in PED height and width 6 months after operation(r=0.218,0.209,P=0.520,0.538).At 1 month after the operation,9 eyes had PED recurrence or different degrees of retinal nerve subepithelial effusion,and PED improved after repeated intravitreal injection of conbercept.At 6 months after opera-tion,subfoveal PED completely disappeared in 3 eyes,and the retina was completely reattached.There was still active exu-dation in the retina of 1 eye.No systemic or severe ocular complications occurred in 13 eyes during the follow-up period.Conclusion Subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the treatment of PCV complicated with sPED can safely and effectively reduce CRT,improve PED,and reduce the damage to the retina caused by long-term PED,but it has no significant effect on the improvement of BCVA at 6 months after the operation.
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Objective To compare the clinical outcomes and retinal volume changes in patients with ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion(BRVO-ME)using optical coherence tomography angiography(OCTA).Methods The clinical data of 34 ischemic BRVO-ME patients(34 eyes,ischemic group)and 21 non-ischemic BRVO-ME patients(21 eyes,non-ischemic group)were retrospectively analyzed.Patients in both groups re-ceived intravitreal injections of ranibizumab.The best corrected visual acuity(BCVA)and retinal volume of the macular ar-ea were assessed before,1 day,1 week,1 month,3 months and 6 months after the treatment.Results The BCVA(log-MAR)at 1 day after the treatment was 0.63±0.37 in the ischemic group and 0.44±0.22 in the non-ischemic group,and the difference was statistically significant(P=0.017).The retinal volumes of the outer retina,the full retina,and the Farafovea and Perifovea subdivisions of the full retina before the treatment were(6.42±1.90)mm3,(8.75±1.82)mm3,(3.20±0.87)mm3 and(5.10±0.89)mm3 in the ischemic group and(5.52±1.57)mm3,(7.83±1.56)mm3,(2.80± 0.71)mm3,and(4.66±0.77)mm3 in the non-ischemic group,respectively;1 day after treatment,they were(4.97± 1.18)mm3,(7.46±1.47)mm3,(2.62±0.60)mm3 and(4.53±0.80)mm3 in the ischemic group and(4.25±0.48)mm3,(6.58±0.56)mm3,(2.26±0.26)mm3 and(4.06±0.40)mm3 in the non-ischemic group,respectively;at 1 week after the treatment,they were(4.40±0.82)mm3,(6.90±0.85)mm3,(2.38±0.36)mm3 and(4.24±0.49)mm3 in the ischemic group and(4.04±0.35)mm3,(6.33±0.49)mm3,(2.15±0.19)mm3 and(3.95±0.35)mm3 in the non-ische-mic group,respectively,and the differences between the two groups were statistically significant(all P＜0.05).The a-mount of retinal volume change from baseline in the outer retina and the full retina was(-2.48±2.38)mm3 and(-2.54±2.38)mm3 in the ischemic group,and(-1.31±1.58)mm3 and(-1.38±1.58)mm3 in the non-ischemic group at 1 month after treatment,respectively,and the differences between the two groups were statistically significant(both P＜0.05).Conclusion Ranibizumab is effective in treating both ischemic and non-ischemic BRVO-ME.The short-term visu-al prognosis is better in the non-ischemic group than the ischemic group,and the retinal volume is higher in the ischemic group than the non-ischemic group.However,no significant difference is observed in the visual prognosis or retinal volume between the two groups after long-term treatment.
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Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.
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Objective:To assess the efficacy and safety of the treat-and-extend (TAE) regimen and pro re nata (PRN) regimen of intravitreal conbercept in polypoidal choroidal vasculopathy (PCV) patients.Methods:A non-randomized controlled study was performed.Ninety-one patients (91 eyes) diagnosed with treatment-na?ve PCV from October 2016 to January 2019 at Department of Ophthalmology, Peking University People's Hospital were enrolled.All the patients received the intravitreal injection of 0.5 mg conbercept.After the initial treatment, the patients were divided into 3+ PRN group and 3+ TAE group according to their willingness.The follow-up time was one year.All the eyes underwent visual acuity test with ETDRS chart, optical coherence tomography (OCT) examination, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Best corrected visual acuity (BCVA), central retinal thickness (CRT), maximum retinal thickness (MRT), pigment epithelium detachment (PED) height, the number and area of polypoidal lesions, the area of retinal hemorrhage and the area of branching vascular network (BVN) were recorded.Treatment interval and injection frequencies during the one-year follow-up were compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by Peking University People's Hospital (No.2020PHB250-01). Written informed consent was obtained from each patient.Results:One-year after treatment, the BCVA improvement in the 3+ PRN group and 3+ TAE group was 5.0(-2.0, 15.0) and 6.0(-1.0, 14.0) letters, respectively, showing no significant difference ( Z=-0.352, P=0.725). No significant differences were found in CRT, MRT and PED height between the two groups ( Z=-0.145, -0.529, -0.985, all at P>0.05). There was no significant difference in polypoidal lesions number, polypoidal lesions area, the number of eyes with different degrees of polyp regression, BVN area and retinal hemorrhage area between the two groups ( Z=-0.502, -0.300, -0.047, -0.265, -1.243, all at P>0.05). After the one-year follow-up, the mean injection frequency of 3+ PRN group was (7.6±0.9) times, which was lower than (8.4±2.0) times of 3+ TAE group, showing a significant difference ( t=2.432, P=0.019). The mean follow-up frequency was (11.3±1.5) times of 3+ PRN group, which was significantly higher than (10.1±1.7) times of 3+ TAE group ( t=3.403, P=0.001). For the 3+ TAE group, 17.1%(6/35) of patients achieved an extension interval of 12 weeks after the first 3 doses, and 48.5%(17/35) of patients achieved an extension interval of 8 weeks or more, with a mean maximum extension interval of (9.5±2.0) weeks.During the follow-up, 10 patients in 3+ PRN group and 8 patients in 3+ TAE group received photodynamic therapy as a rescue treatment. Conclusions:The 3+ PRN and 3+ TAE regimens of intravitreal injection of conbercept combined with photodynamic therapy as a rescue treatment have similar efficacy in visual and anatomical outcomes for PCV patients.3+ TAE regimen has a higher treatment frequency and fewer follow-up visits.
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Secretogranin Ⅲ (SCG3) is a kind of secretory granule widely distributed in tissues and cells with endocrine functions in the human body.As a member of the granin family, it is generally considered to be involved in endocrine and neuroendocrine regulatory activities, and also as a highly disease-selective angiogenic factor that reduces vascular leakage and neovascularization in animal models of diabetic retinopathy and retinopathy of prematurity.In addition, SCG3 also co-expresses with inflammatory factors, anti-brain-derived neurotrophic factors in nerve cells.This article reviewed the current understanding of SCG3 as a secretory granular protein and its granulocyte family, analyzed the distribution of SCG3 in vivo, discussed its role in angiogenesis, and considered the correlation between SCG3 and neovascularization.It focused on the possible role and significance of SCG3 in diabetic retinopathy, especially in relation to microangiopathy, inflammatory factors and retinal neurodegeneration.By comparing the differences between SCG3 and vascular endothelial growth factor (VEGF) in the binding of signaling pathways and related receptors, the effects and advantages of anti-SCG3 drugs in the treatment of DR were prospected.
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Objective To explore the clinical effect of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma.Methods A total of 240 infants with cutaneous hemangioma were randomly divided into the control group(120 cases)and the combined group(120 cases).The control group was treated with timolol maleate,and the combined group was treated with timolol maleate combined with cryotherapy.The clinical efficacy,tumor diameter,levels of serum matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)and the occurrence of adverse reactions of the two groups were compared.Results The total effective rate of the combined group was significantly higher than that of the control group(P<0.05).Compared with before treatment,the tumor diameter 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the tumor diameter 3 months and 6 months after treatment in the combined group decreased more obviously(P<0.05).Compared with before treatment,the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the combined group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the total incidence of adverse reactions such as eczema,ulcer,erosion or redness between the two groups(P>0.05).Conclusion Timolol maleate combined with cryotherapy for infantile cutaneous hemangioma has significant curative effect,which can effectively reduce the levels of serum MMP-9 and VEGF,and shrink the tumor body,with safety and effectiveness.
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Objectives:To observe the repair effect of AKE/GB30 mesh cage loaded with naringin in spinal bone defect model,and explore the mechanism of this biomaterial based on bone morphogenetic proteins(BMPs)-vascular endothelial growth factor(VEGF)signal pathway.Methods:A dental drill was used to make a 7mmx5mmx4mm spinal bone defect model between L5 and L6 vertebrae in 30 New Zealand male rabbits,and AKE/GB30 mesh cages were prepared.The biomechanical properties of AKE/GB30 mesh cages loaded with naringin were tested,and their in vitro drug release behavior was measured.New Zealand rabbits that were successfully modeled were randomly divided into three groups using a randomly digital table method,namely,blank group,autologous bone graft group,and bone graft biomaterial+naringin combined group.Except the blank group,autologous bone transplantation and AKE/GB30 mesh cage loaded with naringin were used for repair.At 6 weeks and 12 weeks after surgery,5 rabbits were taken from each group,and the bone repair status[including bone volume/tissue volume(BV/TV),bone trabecular thickness(Tb.Th)and bone trabecular number(Tb.N)]were detected by micro computed tomography(Micro CD.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to detect the expressions of bone morphogenetic protein 2(BMP2),VEGF,Runt related transcription factor 2(RUNX2),alkaline phosphatase(ALP),and osteocalcin(OCN)messenger ribonucleic acid(mRNA).Immunoblotting assay(WB)was used to detect the expressions of BMP2,VEGF,RUNX2,ALP,and OCN proteins in bone tissues.Results:AKE/GB30 mesh cages had been successfully manufactured,and its characteristic testing results met the requirements for repairing spinal bone defects.The AKE/GB30 mesh cage loaded with naringin had a maximum compressive strength of 28MPa and a maximum resistance pressure of 15N.At 6 weeks,its cumulative release rate reached(98.15±1.47)％.After 12 weeks,the BV/TV,Tb.Th,and Tb.N,as well as the mRNA and protein expressions of BMP2,VEGF,RUNX2,ALP,and OCN in bone tissues of each group were higher than those after 6 weeks(P＜0.05).The above indicators in the autologous bone graft group and the bone graft biomaterial+naringin combined group were higher than those in the blank group(P＜0.05),and there were no significant differences in the above indicators between the autologous bone graft group and the bone graft biomaterial+naringin combined group(P＞0.05).Conclusions:The effect of AKE/GB30 cage loaded with naringin in repairing spinal bone defect models is equivalent to that of autologous bone graft,which is presumed to achieve by promoting the expressions of BMP2,VEGF,RUNX2,ALP,and OCN.
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Objective:To investigate the effect of exercise preconditioning on angiogenesis in ischemic brain tissue in rats with cerebral ischemia-reperfusion injury in the view of VEGF/VEGFR2/dock6 signaling pathway. Method:SD male rats were divided into sham group,model group and exercise preconditioning group by ran-dom number table method,with 18 rats in each group.The sham operation group and the model group were not given any treatment,while the exercise preconditioning group was given adaptive running training for 3 days at a speed of 10 m/min,once a day for 20 minutes each time.After the adaptive training,the exercise preconditioning group was given formal running training for 3 weeks,continuous training for 6 days a week,rest for 1 day,electric treadmill slope of 0°,speed of 15m/min,30min/d.Model group and exercise precondi-tioning group were modified to prepare the middle cerebal artery occlusion(MACO)models by Koizumi thread method,while sham operation group only given skin cutting without thread insertion.Zea longa score and modi-fied neurological severity score(mNSS)were used to score neurological deficit in rats,the relative infarct size of the brain was detected by TTC staining,the morphological changes of the ischemic cerebral cortex was ob-served by HE staining,the expression of CD31 in ischemic cerebral cortex was detected by immunohistochemis-try and the expressions of VEGFA,VEGFR2,Dock6 in ischemic cerebral cortex were detected by western blot. Result:①Zea-Longa scoring:after awaking from anesthetizati,compared with the sham group,the Zea-Longa scores of the other two groups were increased(P＜0.01),and there was no statistical significance in the Zea-Lon-ga scores between the two groups.At 72 hours after reperfusion,compared with the sham group,the Zea-Longa score of the rats in the model group was significantly increased(P＜0.01);compared with the model group,the Zea-Longa score of the rats in the exercise preconditioning group was significantly decreased(P＜0.05).②mNSS scoring:At 72 hours after reperfusion,compared with the sham group,the mNSS score of the rats in the mod-el group was significantly increased(P＜0.01);compared with the model group,the mNSS score of the rats in the exercise preconditioning group was significantly decreased(P＜0.05).③TTC staining:Compared with the sham group,the cerebral infarction volume in the model group was increased(P＜0.01),and compared with the mod-el group,the cerebral infarction volume in the exercise preconditioning group was decreased(P＜0.05).④ HE staining:Compared with the sham group,the model group rats appeared significant pathological changes in the cerebral cortex on the ischemic side.Compared with the model group,the pathological changes of the cerebral cortex on the ischemic side of the rats in the exercise preconditioning group were alleviated.⑤ Immunohisto-chemistry of CD31:Compared with the sham group,the expression of CD31 in the ischemic cerebral cortex of the model group was significantly increased(P＜0.05).The expression of CD31 in the ischemic cerebral cortex of the exercise preconditioning group was further increased(P＜0.05).⑥Western blot of VEGF,VEGFR2 and Dock6:Compared with the sham group,the expressions of VEGF(P＜0.05),VEGFR2(P＜0.05)and Dock6(P＜0.01)in the ischemic cerebral cortex of the model group were significantly increased;compared with the model group,the expressions of VEGF(P＜0.05),VEGFR2(P＜0.05)and Dock6(P＜0.01)in the ischemic cerebral cor-tex of the exercise preconditioning group were further increased. Conclusion:Exercise preconditioning can effectively promote angiogenesis after cerebral ischemia and reduce cerebral ischemia-reperfusion injury,which may be related to the activation of VEGF/VEGFR2/Dock6 signaling pathway.
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Objective:To explore the correlation between myocardial damage and vascular endothelial growth factor (VEGF), red blood cell distribution width (RDW), and myocardial enzyme spectrum in children with severe mycoplasma pneumoniae pneumonia.Methods:Sixty children with severe mycoplasma pneumoniae pneumonia and myocardial damage admitted to Jining Medical University from January 2019 to December 2020 were selected as the observation group, and 60 children with severe mycoplasma pneumoniae pneumonia admitted during the same period were selected as the control group. The differences in clinical data and imaging features between the two groups were compared. Pearson correlation analysis was used for correlation analysis; The logistic regression method was applied to analyze the influencing factors of myocardial damage in children with severe mycoplasma pneumoniae pneumonia. The value of VEGF and RDW in predicting myocardial damage in children with severe mycoplasma pneumoniae pneumonia was analyzed using receiver operating characteristic (ROC) curves.Results:The levels of C-reactive protein (CRP), procalcitonin (PCT), VEGF, RDW, creatine kinase isoenzyme (CK-MB), creatine kinase (CK), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH) in the observation group were significantly higher than those in the control group (all P<0.05), and the duration of fever, application of macrolide drugs, and glucocorticoid application time were significantly longer than those in the control group (all P<0.05). There was no statistically significant difference in pulmonary imaging characteristics between the observation group and the control group (all P>0.05). The VEGF and RDW in the observation group were positively correlated with CK-MB and cTnI (all P<0.05). Logistic regression analysis showed that duration of fever, VEGF, RDW, and duration of macrolide drug use were the influencing factors for myocardial damage in children with severe mycoplasma pneumoniae pneumonia (all P<0.05). The area under the ROC curve of VEGF combined with RDW in predicting myocardial damage in children with severe mycoplasma pneumoniae pneumonia was 0.899, significantly higher than that predicted by VEGF and RDW alone (all P<0.05). Conclusions:The serum VEGF and RDW levels in children with severe mycoplasma pneumoniae pneumonia accompanied by myocardial damage are elevated and positively correlated with myocardial enzyme spectrum indicators, which has certain application value in predicting myocardial damage.
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Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.