Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection

AIM:To explore the efficacy of minimally invasive vitrectomy(MIV)with or without internal limiting membrane(ILM)peeling on the treatment of diabetic macular edema(DME)in proliferative diabetic retinopathy(PDR)combining with preoperative anti-vascular endothelial growth factor(anti-VEGF)injection.METHODS:Totally 132 eyes(132 patients)diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye Hospital.The single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 eyes.Anti-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to 3y.Best-corrected visual acuity(BCVA),central retinal thickness(CRT),total macular volume(TMV),macular edema(ME)severity,intraocular pressure(IOP),and complications were recorded.Prognostic factors of visual acuity following ILM peeling were analyzed.RESULTS:The BCVA was higher than preoperative values at 1,3,6,and 12mo after surgery in both groups(all P<0.05).At 6 and 12mo,the BCVA of the combined group was significantly higher than that of the MIV only group(0.52±0.23 v/s 0.64±0.29 IogMAR,P=0.011 in 6mo;0.41±0.25\/s 0.52±0.25 IogMAR,P=0.008 in 12mo).Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1^(st) month(lmo 397.65±106.18 vs 451.94±118.88 μm in MIV only group;388.88±108.68 v/s 464.36±111.53 μm in combined group;both P<0.05)and decreased gradually.The differences between the two groups were statistically significant at 3,6,and 12mo(P=0.004,0.003,0.00 respectively).The TMV was decreased from the 3^(rd) month in the single treatment group(3mo 11.14±1.66 vs 12.20±2.09 mm^(3),P<0.05).At 12mo,the proportion of eyes with edema that had CRT more than 350μm was significantly lower than before surgery(13.24%vs 77.94%in MIV only group;1.56%vs 81.25%in combined group;both P<0.05).There was no significant difference in the recurrence incidence of macular epiretinal membrane,ME,transient IOP increase,vitreous rebleeding,or traction retinal detachment between the two groups.BCVA after ILM excision was positively correlated with the CRT and ME degree before and after surgery(r=0.430,0.485,respectively;P<0.05).CONCLUSION:MIV combined with ILM peeling accelerates the absorption of ME,improves vision,reduces the postoperative CRT and TMV,and reduces the recurrence rate of postoperative ME.

Macular hole closure following anti-vascular endothelial growth factor injection in an eye with myopic choroidal neovascularization

Dear Editor,I am Cheolmin Yun,from the Department of Ophthalmology,Korea University College of Medicine.I write to present a case report of a female patient with a myopic patient suffering from atrophic choroidal neovascularization（CNV）and a full thickness macular hole（FTMH）,who was treated with an intravitreal anti-vascular endothelial growth factor （VEGF） injection without vitrectomy.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet,China

AIM: To evaluate the outcomes of intravitreal antivascular endothelial growth factor(anti-VEGF) agents for patients with retinal vein occlusion(RVO) related-macular edema(ME) in Tibetan.METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients(93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People’s Hospital from Jan 2018 to December 2019 were collected.RESULTS: The mean patient age was 56.8±10.6y, 45(50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity(BCVA) significantly increased(52.2±21.8 letters) in comparison with the baseline(38.2±24.1 letters, P<0.001);while the central retinal thickness(CRT) significantly reduced(245.5±147.6 μm) in comparison with the baseline(504.1±165.2 μm, P<0.001). The 43.0% of the eyes gained≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted.CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.

Efficacy and mechanism of anti-vascular endothelial growth factor drugs for diabetic macular edema patients

BACKGROUND Diabetes is a serious public health concern in China,with 30%of patients developing retinopathy,and diabetic macular edema(DME)having the biggest impact on vision.High blood glucose level can cause retinal cell hypoxia,thus promoting vascular endothelial growth factor(VEGF)formation and increasing vascular permeability,which induces DME.Moreover,cell hypoxia can accelerate the rate of apoptosis,which leads to the aging of patients.In severe cases,optic cell apoptosis or retinal fibrosis and permanent blindness may occur.AIM To investigate and compare the efficacy,mechanism,and differences between two anti-VEGF drugs(Compaq and ranibizumab)in DME patients.METHODS Ninety-six patients with DME who attended our hospital from April 2018 to February 2020 were included and randomly divided into two groups(Compaq group and ranibizumab group).The groups received vitreal cavity injections of 0.5 mg Compaq and 0.5 mg ranibizumab,respectively,once a month.The best corrected visual acuity(BCVA),intraocular pressure(IOP),macular retinal thickness(CMT),macular choroidal thickness(SFCT),foveal no perfusion area(FAZ),superficial capillary density,deep capillary density,treatment effect,and adverse reactions were compared before and after treatment and between the two groups.RESULTS Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated BCVA in both groups(P>0.05).BCVA decreased in the Compaq group 3 mo after treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there was no statistically significant difference in the estimated IOP in either group(P>0.05).Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated CMT,SFCT,or FAZ in either group(P>0.05).CMT and SFCT values decreased in the Compaq group 3 mo post-treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there were no statistically significant differences in vascular density in the shallow or deep capillary plexi of the fovea,parafovea,or overall macular area between the two groups(P>0.05).Marked efficient,effective,and invalid rates were 70.83%and 52.08%,27.08%and 39.58%,and 2.08%and 8.33%in the Compaq and ranibizumab groups,respectively.The differences between the two groups were statistically significant(P<0.05).CONCLUSION Anti-VEGF drugs can effectively improve CMT and SFCT,without affecting microcirculation,thus providing an effective and safe treatment for patients with DME.

Combined therapy versus anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy： a Meta-analysis

AIM： To evaluate the efficacy and safety of anti-vascular endothelial growth factor （VEGF） combined with photodynamic therapy （PDT） versus anti-VEGF monotherapy for polypoidal choroidal vasculopathy （PCV）. METHODS： We conducted a Meta-analysis of 9 studies to compare the efficacy and safety between combined therapy and anti-VEGF monotherapy for PCV. The programs of RevMan 5.3 and Stata 12.0 were used to analyze data. RESULTS： The best corrected visual acuity （BCVA） in combined therapy group were significantly better than those of anti-VEGF monotherapy group at 6, 24 and 36mo, with pooled weighted means differences （WMDs） of 0.12 （0.06, 0.18）, 0.25 （0.12, 0.38） and 0.28 （0.13, 0.43）, respectively. The central retinal thickness （CRT） reductions in combined therapy group were higher than that in anti- VEGF monotherapy group at 1, 3, 6 and 9mo, with pooled WMDs of 63.90 （20.41, 107.38）, 33.47 （4.69, 62.24）, 30.57 （0.12, 60.01） and 28.00 （2.51, 53.49）, respectively. The regression rate of polyps in combined therapy group was much higher than that in anti-VEGF monotherapy group [RD： 0.47 （0.26, 0.68）; P〈0.0001]. The adverse event retinal hemorrhage did not differ significantly between the two groups. CONCLUSION： Our findings clearly document that anti- VEGF combined with PDT is a more effective therapy for PCV compared with anti-VEGF monotherapy. Furthermore, combined therapy does not increase the incidence of retinal hemorrhage.

Antitumor and antiangiogenic activities of anti-vascular endothelial growth factor hairpin ribozyme in human hepatocellular carcinoma cell cultures and xenografts

AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.

Anti-vascular endothelial growth factor treatment for retinopathy of prematurity

Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.

Does Anti-Vascular Endothelial Growth Factor Treatment Delay Photoreceptor Maturation in Preterm Infants?

Purpose: To investigate the effects of intravitreal anti-vascular endothelial growth factor (VEGF) for treatment of type-1 or aggressive posterior retinopathy of prematurity (ROP) on photoreceptor maturation in preterm infants using spectral domain optical coherence tomography (SD-OCT). Methods: A study group of 36 patients with ROP treated with anti-VEGF therapy was compared to a control group of 80 patients with ROP. All patients had undergone SD-OCT imaging at least once between 40 and 44 weeks post-menstrual age (PMA). Two imaging specialists evaluated the images for ellipsoid zone (EZ) development, cystoid macular edema (CME), sub-retinal fluid (SRF) at the fovea, and cone outer segment tips (COST). The outer nuclear layer thickness and the distance from the EZ to the central fovea was measured. Results: EZ development was observed in 18 (50%) patients in the study group and 68 (85%) in the control group (p = 0.002). CME was observed in 17 (47.2%) patients in the study group and 17 (21.2%) in the control group. The distance between the EZ and central fovea was 868 ± 440 μm in the study group and 725 ± 380 μm in the control group (p = 0.02). COST was not observed in any patient. Regression analysis indicated that anti-VEGF treatment and CME affect EZ development. Conclusions: Early photoreceptor maturation is correlated with preterm birth week but not ROP stage. Anti-VEGF treatment delays photoreceptor maturation in preterm infants.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP.METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab.Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment.Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment.Adverse outcomes included progression to retinal detachment.RESULTS The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 years.CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

Progress of anti-vascular endothelial growth factor therapy for ocular neovascular disease： benefits and challenges

publication. Study selection Clinical trials and case studies presented at medical conferences and published in peer-reviewed literature in the past decade were reviewed. Results Anti-VEGF agents have manifested great potential and promising outcomes in treating ocular neovascularization, though some of them are still used as off-label drugs. Intravitrea~ injection of anti-VEGF agents could be accompanied by devastating ocular or systemic complications, and intimate monitoring in both adult and pediatric population are warranted. Future directions should be focused on carrying out more well-designed large-scale controlled trials, promoting sustained duration of action, developing safer and more efficient generation of anti-VEGF agents. Conclusions Anti-VEGF treatment has proved to be beneficial in treating both anterior and posterior neovascular ocular diseases. However, more safer and affordable antiangiogenic agencies and regimens are warranted to be explored.

Anti-vascular endothelial growth factor： the future treatment of choroidal neovascularization in pathologic myopia

-yopia is the most common refractive disorder. High .myopia affects 27%-33% of all myopic eyes inAsia.1,2 ;The pathologic myopia （PM） is the most severe vision-threatening phenotype of high myopia.3 It is also the second most common cause of choroidal neovascularization （CNV） in Asia. Unlike age-related macular degeneration （AMD） which mostly effecting elders, PM causes severe vision loss in young adults, resulting in a significant impairment of their working ability.4 PM has become the second leading cause of low vision and blindness particularly among those aged at 40-49 years in some Asia countries.

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage

BACKGROUND Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and cortisol(Cor)and the prognosis of patients with hypertensive cerebral hemorrhage.METHODS A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group.Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group.Peripheral venous blood was collected,and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay.RESULTS A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment(P<0.05).Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group.Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses.Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage(P<0.05).CONCLUSION Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

Vascular endothelial growth factor protein and gene delivery by novel nanomaterials for promoting liver regeneration after partial hepatectomy

Partial hepatectomy(PH)can lead to severe complications,including liver failure,due to the low regenerative capacity of the remaining liver,especially after extensive hepatectomy.Liver sinusoidal endothelial cells(LSECs),whose proliferation occurs more slowly and later than hepatocytes after PH,compose the lining of the hepatic sinusoids,which are the smallest blood vessels in the liver.Vascular endothelial growth factor(VEGF),secreted by hepatocytes,promotes LSEC proliferation.Supplementation of exogenous VEGF after hepatectomy also increases the number of LSECs in the remaining liver,thus promoting the reestablishment of the hepatic sinusoids and accelerating liver regeneration.At present,some shortcomings exist in the methods of supplementing exogenous VEGF,such as a low drug concentration in the liver and the reaching of other organs.Moreover,VEGF should be administered multiple times and in large doses because of its short half-life.This review summarized the most recent findings on liver regeneration and new strategies for the localized delivery VEGF in the liver.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value

Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammatory fat deposition),nonalcoholic fatty hepatitis,liver fibrosis,and so on,which may cause liver cirrhosis,liver failure,and even liver cancer in the later stage of disease progression.At present,the pathogenesis of NAFLD is still being studied.The"two-hit"theory,represented by lipid metabolism disorder and inflammatory reactions,is gradually enriched by the"multiple-hit"theory,which includes multiple factors,such as insulin resistance and adipocyte dysfunction.In recent years,vascular endothelial growth factor B(VEGFB)has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases,such as obesity and type 2 diabetes.This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism.In conclusion,the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

Predictors of anti-vascular endothelial growth factor treatment responses in macular edema following central vein occlusion

Retinal vein occlusion （RVO） ranged the second common cause of retinal vascular disease, consisting of central retinal vein occlusion （CRVO） and branch retinal vein occlusion （BRVO） Although the prevalence of CRVO was one-third of BRVO, it associated with worse prognosis both before and after the anti-vascular endothelial growth factor （VEGF） regimes came into clinic use. A recent pooled age- and sex-standardized analysis showed that the prevalence was 0.8 per 1 000 （CI： 0.61-0.99） for CRVO around the world. Similarly, in our country, the 10-year incidence of CRVO in Beijing （2001-2011） was 0.3±0.1 per 100 persons.