Objective To investigate the possibility of constructing eukaryoticexpression vector for human angiopoietin 1（hAng-1），transfecting it to bonemarrow mesenchymal stem cells (MSCs) so as to repair bone defect. Methods The eukaryotic expression vector pcDNA3-hAng-1 was constructed by recombinant DNA technique, transfected into MSCs by liposome DOTAP, and selected with G418. The hAng-1 expression of mRNA and protein was detected by reverse transcript-PCR and Western Blot. Results After the recombinant eukaryotic expressionvector for hAng-1 was digested with Xho-I and BamH-I, electrophoresis revealed 1.4 kb fragment for hAng-1 gene and 5.4 kb fragment for pcDNA3 vector. In the transfected MSCs, the mRNA and protein expression of hAng-1 gene were detected with reverse transcriptPCR and Western Blot. Conclusion The constructed eukaryotic expression vector hAng-1 could be expressed in the transfected MSCs, thus to provide the basis for bone repair with tissue engineering.
Objective To observe the effects of intravitreal injection of conbercept for aggressive posterior retinopathy of prematurity (AP-ROP). Methods It is a retrospective case study. Twenty-one patients (40 eyes) with AP-ROP were enrolled in this study. There were 9 males (18 eyes) and 12 females (22 eyes), with the mean gestational age of (28.30±1.79) weeks and the mean birth weight of (1 021.40±316.70) g. All the lesions of 40 eyes were located in posterior zone, with 24 eyes in zone I and 16 eyes in zone II. All the eyes were treated with intravitreal injection of conbercept 0.025 ml (0.25 mg). During follow-up, nonresponders or patients with deterioration were retreated with intravitreal injection of conbercept or photocoagulation; patients with progressive deterioration to stage 4 had received vitrectomy. At the 1, 2, 4, 8, 12, 16, 20, 24 weeks after treatments, the disappearance or decrease of retinal vessel tortuosity and neovascularization, and the growth of the normal retinal vessels toward the peripheral retina were evaluated. Results Thirty-six eyes were cured for only one injection, the cured rate was 90.00%. However, 2 eyes (5.00%) had progressed to stage 4 with contractive retinal detachment, which underwent vitrectomy. Two eyes (5.00%) had received twice injections, whose remaining avascular zone area treated by photocoagulation. No major systemic or ocular complications after injection appeared. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-up. Conclusion Intravitreal injection of conbercept is effective in the treatment of AP-ROP.
ObjectiveTo compare the short-term efficacy of conbercept and ranibizumab for macular edema in central retinal vein occlusion (CRVO)and explore the relationship between the integrity of ellipsoidal zone and visual acuity. MethodsForty-four eyes of 44 patients with macular edema in CRVO were enrolled into this retrospective and comparative study. There were 15 eyes of 15 males, 29 eyes of 29 females; age ranged from 49-61 years old,with an average age of (54.65±3.10) years. All patients were examined with best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp, fundus photograph, fundus fluorescein angiography (FFA), optical coherence tomography(OCT). BCVA were examined with interactional visual chart and recorded with logarithm of the minimum angle of resolution acuity. Twenty-three eyes were intravitreal injected with conbercept 0.5 mg (group A) and 21 eyes were intravitreal injected with ranibizumab 0.5 mg (group B). There was no statistical difference of age (t=-1.41), gender (χ2= 0.55),the percentage of hypertension patients (χ2=0.27), average BCVA (t=-2.06), IOP (t=-2.52), central macular thickness (CMT) (t=-1.96), number of different integrity of ellipsoidal zone patients (χ2=1.00) and number of different types of macular edema patients (χ2=1.03) among the two groups (P > 0.05). The change in BCVA and CMT at 3, 6 months between the two groups were compared. The relationship between BCVA at 6 months and BCVA, CMT at baseline were explored. The relationship between three groups of ellipsoidal zone and BCVA at baseline were evaluated. The change of BCVA after treatment between the three groups of ellipsoidal zone were Compared. The number of intravitreal injections between two groups was compared. ResultsDuring the 3, 6 months after treatment, the mean BCVA were all improved with statistically difference in group A (t=5.13, 7.39; P < 0.05) and group B (t=6.60, 11.52; P < 0.05). There was no significant difference of BCVA at 3, 6 moths between group A and group B (t=-0.99, -0.40; P > 0.05). During the 3, 6 months after treatment, the mean CMT were all decreased with statistically difference in group A (t=11.58, 15.96; P < 0.05) and group B (t=18.77, 35.16; P < 0.05). There was no significant difference of CMT at 3, 6 months between group A and group B (t=-1.52, -1.63; P > 0.05). In both groups,BCVA at 6 months was related to BCVA at baseline (r= 0.44, 0.62; P < 0.05), but not related to CMT at baseline (r=0.19, 0.01; P > 0.05). In the two groups, BCVA at baseline was related to the integrity of ellipsoidal zone (r=0.97, 0.70; P < 0.05). There was statistical difference of the number of intravitreal injections in the two groups (t=-6.88, P < 0.05). There was no systemic or ocular serious side effects during the follow up. ConclusionsComparing to ranibizumab, conbercept has the same effective to the treatment of macular edema in CRVO, but the number of intravitreal injections is less. The integrity of ellipsoidal zone is related to BCVA.
Objective?To investigate the osteogenesis effects of angiopoietin 1 (Ang-1) gene transfected bone marrow mesenchymal stem cells (BMSCs) seeded on β tricalcium phosphate (β-TCP) scaffolds (tissue engineered bone) with platelet-rich plasma (PRP).?Methods? BMSCs were isolated from bone marrow tissue of rabbits. The Ang-1 gene was transfected into the BMSCs at passage 2 by lentivector, which were seeded on β-TCP scaffolds with PRP (0.5 mL) after 48 hours of transfection. Bilateral radial segmental bone defects (15 mm in length) were created in 20 3-month-old New Zealand rabbits. Then the tissue engineered bone with the Ang-1 gene transfected BMSCs (experimental group) and untransfected BMSCs (control group) were implanted into the defects in the right and left radius, respectively. X-ray, histology, immunohistochemistry, and biomechanics observations were done at 2, 4, 8, and 12 weeks after operation.?Results?In vitro, the transfected rate was over 90% and RT-PCR showed that the Ang-1 expression were significantly increased after transfection. The X-ray films showed that some callus formed at 4 weeks, partial bony union was observed at 8 weeks, and complete union at 12 weeks in experimental group; and bone union was not observed at 12 weeks in control group. HE staining showed that capillary appeared at 8 weeks and more capillaries were observed in new bone at 12 weeks in experimental group; only a few capillaries were observed at 12 weeks in control group. At 8 and 12 weeks, the microvascular density were (50.1 ± 7.8) /mm2 and (66.1 ± 3.5) /mm2 in experimental group and were 0 and (30.3 ± 7.2)/mm2 in control group, showing significant differences between 2 groups at 12 weeks (Z= —2.107, P=0.031). Immunohistochemistry examination showed that the positive cells can be found at 8 weeks in experimental group. And the biomechanical analysis showed that maximum loads of experimental group were significantly higher than those of control group in three-point bending test and compression test at 12 weeks (P lt; 0.05).?Conclusion?The tissue engineered bone with PRP and Ang-1 can increase the osteogenic properties by enhancing capillary regeneration, thus it can be used to repair radial segmental bone defects of rabbit.
Objective To evaluate the role for integrins in tumor angiogenesis. MethodsLiteratures in recent years were reviewed. ResultsIntegrins played an important role in tumor angiogenesis and integrins had a close relation to vascular growth factors. Conclusion Inhibitors of integrins will be a promising way to cure tumors.
Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.
ObjectiveTo evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs combined with retinal laser photocoagulation and anti-VEGF drugs alone in the treatment of retinal vein occlusion (RVO) combined with macular edema (ME). MethodsA evidence-based medicine study. Retinal vein occlusion (obstruction), macular edema, anti-vascular endothelial growth factor, bevacizumab, ranibizumab, conbercept, aflibercept, and retinal laser photocoagulation were the Chinese and English search terms. Related literature was searched in China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Embase, Cochrane Library. RVO combined with ME was selected as the research object, and the treatment plan was a clinical randomized controlled study comparing intravitreal injection of anti-VEGF drugs combined with laser photocoagulation and anti-VEGF drugs alone. The search time range was from January 2011 to February 2021. Repeated, incomplete or irrelevant literature, case reports and review literature were excluded. Review Manager 5.4 statistical software was used to conduct a meta-analysis of the literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were selected as the estimated value of effect size, and the fixed effect model was used for analysis. The evaluation indicators were best corrected visual acuity (BCVA), center macular thickness (CMT), and the number of injections. ResultsAccording to the search strategy, 461 articles were initially retrieved, and 21 articles were finally included for meta-analysis. A total of 1156 patients were enrolled, of which 576 were treated with anti-VEGF drugs combined with laser photocoagulation (combined treatment group), and 580 were treated with anti-VEGF drugs alone (drug treatment group). Meta-analysis results showed that there was no statistically significant difference in BCVA and CMT between the drug treatment group and the combination treatment group at 6, 9, and 12 months after treatment (BCVA: WMD =－0.82, 95%CI －2.38-0.74, P=0.30; CMT: WMD=－3.12, 95%CI －17.25-11.01, P=0.67). For patients with branch retinal vein occlusion and ME, combined therapy can reduce the number of injections more effectively than drug therapy alone (WMD=－0.80, 95% CI －1.18-－0.42, Z=4.10, P＜0.000 1). ConclusionCompared with pure intravitreal injection of anti-VEGF drugs, combined retinal laser photocoagulation can not better improve BCVA and CMT in patients with RVO and ME. For patients with branch retinal vein occlusion and ME, combined retinal laser photocoagulation can effectively reduce the resistance. The number of VEGF injections.
ObjectiveTo observe the effect of intravitreal injection of Conbercept with two different doses in the treatment of retinopathy of prematurity (ROP）and explore the clinical feasibility of ROP treatment by lower dose conbercept.MethodsThis was a prospective study. The premature infants were enrolled with pre-threshold type 1, threshold and acute aggressive posterior retinopathy of prematurity (AP-ROP) from March 2018 to June 2019, who received fundus screening in neonatal intensive care unit (NICU) of Henan Provincial People's Hospital, Henan Eye Hospital. They were randomly divided into two groups. The group A (lower dose group) were received intravitreal injection of conbercept with 0.15 mg/0.015 ml, and those in group B (control group) were received intravitreal injection of conbercept with 0.25 mg/0.025 ml. We checked and recorded the lesion area, stage, scope (according to the clock range), additional lesion (plus), etc. Fundus examination should be performed with the pediatric wide-field fundus imaging system within 7 days after treatment. It was used to observe the plus disese, ridge, regression of neovascularization on ridge, and development of retinal vessels to serrated edge or scarring. The follow-up period was at least 24 weeks. The effect evaluation was divided into recovery, improvement, recurrence and aggravation.ResultsThe 43 ROP subjects (84 eyes) were enrolled including 21 cases (40 eyes) in group A and 22 (44 eyes) in group B. There was no significant difference between the two groups in gender (χ2=1.169), birth age (t=0.283), birth weight (t=0.547), hospitalization days in NICU (t=1.187), first examination time (t=1.811), first injection time (t=0.492), follow-up time (t=0.899) and ROP condition (χ2=0.854) (P>0.05). In group A, 21 eyes (52.5%) were cured, 17 eyes (42.5%) were improved, 2 eyes (5.0%) were recurred, and no aggravating cases were found. In group B, 24 eyes (54.5%) were cured, 14 eyes (31.8%) were improved, 6 eyes (13.6%) were recurred, and no aggravating cases were found. There was no significant difference of the cure rate (χ2=2.210, P>0.05) and effective (recovery and improvement) rate (χ2=1.814, P=0.269）between two groups after the first injection.ConclusionIntravitreal injection of conbercept with the two doses should be effective in the treatment of ROP.