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Objective:To investigate the protective effect of asiatic acid (AA) on blood-retinal barrier (BRB) in diabetic rats and its possible mechanism.Methods:Ninety-six healthy 8-week-old male SD rats were randomly divided into normal control group, diabetes group, low-dose AA group and high-dose AA group, with 24 rats in each group.Intraperitoneal injection of streptozocin (STZ) was used to establish diabetes model.One month after the establishment of the model, the low-dose AA group and the high-dose AA group were given intragastrical administration of 37.5 mg/kg AA and 75.0 mg/kg AA, respectively, once a day according to grouping.The normal control group and the diabetes group were administrated with the same amount of 0.5% sodium carboxymethyl cellulose.The body weight of the rats were weighted at week 0, 1, 2, 3, 4 after intragastrical administration.Blood was taken from the tail vein and the blood glucose level was measured.The retina was obtained one month following the administration.Pathological changes of the rats retina were detected by hematoxylin-eosin (HE) staining.Evan's blue quantitative method was used to detect the damage of blood-retinal barrier (BRB). Immunofluorescence staining was performed to detect the distribution of Occludin, Notch1, Jagged canonical Notch ligand 1 (JAG1) and Delta like canonical Notch ligand 4 (DLL4) in retina.The mRNA and protein expressive levels of Occludin, Notch1, JAG1 and DLL4 were detected by Real-time PCR and Western blot.The study protocol was approved by a Scientific Research and Clinical Trial Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-228). The use and care of animals complied with the Guide for the Care and Use of Laboratory Animals of National Institutes of Health and the 3R rules.Results:At 4 weeks after intragastrical administration, the body weight of the high-dose AA group was significantly higher than that of the diabetes group, and the blood glucose values were significantly lower in the high-dose AA group and the low-dose AA group in comparison with the diabetes group (all at P<0.05). The cells were arranged orderly with clear layered structure in the normal control group.In the diabetes group, the retina was thicker than that of the normal control group, with a thicker outer nuclear layer, disordered cell arrangement and unclear layered structure.Compared with the diabetes group, the total retinal thickness and structure were obviously improved in the low-dose AA group and the high-dose AA group.Evan's blue leakage in retina was (3.07±1.30), (13.73±3.88), (9.57±2.69) and (6.55±1.61)ng/mg in the normal control group, the diabetes group, the low-dose AA group and the high-dose AA group, respectively.There was a significant difference in leakage of Evan's blue among the four groups ( F=18.50, P<0.01), among which the leakage of Evan's blue dye in the high-dose AA group was significantly lower than that of the diabetes group ( P<0.01). Compared with the diabetes group, there was significantly higher relative expression level of Occludin protein and significantly lower relative expression levels of Notch1, JAG1 and DLL4 proteins in the other three groups (all at P<0.05). The relative expression level of Occludin protein was significantly higher and the relative expression levels of Notch1, JAG1 and DLL4 proteins were significantly lower in the high-dose AA group than those in the low-dose AA group (all at P<0.05). Compared with the normal control group, the Occludin mRNA expression level was significantly decreased and the expression levels of Notch1, JAG1 and DLL4 mRNA were significantly increased in the diabetes group and low-dose AA group (all at P<0.01). The Occludin mRNA expression level was higher and the Notch1 mRNA expression level was lower in the high-dose AA group than those in the diabetes group and the low-dose AA group, and the expression levels of JAG1 and DLL4 mRNA were lower in the high-dose AA group in comparison with the diabetes group, and the differences were statistically significant (all at P<0.05). Conclusions:Asiatic acid might play a protective role on BRB in diabetic rats by inhibiting Notch1 signaling pathway.
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Objective:To observe the effect of attenuated-dose aflibercept in the treatment of retinopathy of prematurity(ROP).Methods:A non-randomized controlled study was conducted, and 76 eyes of 38 ROP pediatric patients treated in First Affiliated Hospital of Zhengzhou University from December 2018 to May 2020 were enrolled.According to the requirements of their guardians, the patients were divided into ranibizumab group with 42 eyes of 21 cases and attenuated-dose aflibercept group with 34 eyes of 17 cases, and received intravitreal injection of ranibizumab 0.025 ml (0.25 mg) or aflibercept 0.012 5 ml (0.5 mg) according to grouping respectively.Retcam fundus photography was used to observe the treatment response at 1 week, 2, 4 weeks and 2, 3, and 6 months after treatment, and the effective rate at the end of follow-up was calculated.The intraocular pressure was measured with Icare PRO magnetic rebound tonometer at 1 minute, 10, and 30 minutes after injection. The ocular and systemic complications were observed during the 6-month follow-up period.All the guardians signed the informed consent prior to treatment.This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2020-KY-228).Results:The effective rates of single ranibizumab and attenuated-dose aflibercept were 90.5% (38/42) and 88.2% (30/34), respectively, with no significant difference between the two groups ( χ2=0.10, P=0.75). The intraocular pressure of the ranibizumab group at 1 minute and 10 minutes after the operation were higher than those of the attenuated-dose aflibercept group, and the difference was statistically significant (both at P<0.01). The intraocular pressure recovered to the baseline level at 30 minutes after the operation.In the ranibizumab group, 4 eyes were ineffective after a single injection, among which 2 eyes were effective after second intravitreal injection of ranibizumab and 1 eye was effective after retinal laser photocoagulation treatment and 1 eye underwent vitrectomy due to the progress of retinal detachment one week after intravitreal injection, and the posterior retina reattached well.In the attenuated-dose aflibercept group, 4 eyes did not respond to treatment, of which 3 eyes were effective after second intravitreal injection of aflibercept, and 1 eye was effective after retinal laser photocoagulation.No ocular or systemic complications were observed during the followed-up period. Conclusions:Reduced dose of aflibercept is safe and effective in the treatment of ROP, and has little influence on intraocular pressure.
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Objective To summarize continuous veno- venous hemofiltration (CVVH) treatment of infants with complex congenital heart disease in children with acute renal failure after treatment. Methods A retrospective analysis was carried out in six cases of infants with congenital heart disease with application of CVVH. The children were given monitoring and anticoagulant treatment. The renal function, electrolytes and urine volume were compared before and after the treatment. Results The amount of urine increased, blood circulation and electrolytes remained stable in six patients 17.5-135.0 hours after CVVH. Conclusions The CVVH therapy can be applied to treat infants with congenital heart disease complicated with acute renal failure, but CVVH treatment should focus on anticoagulants and blood volume since complicated state of illness, low age, low body weight of children patients.