Study of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway has been becoming more and more popular.This pathway widely exists in kinds of cells of human being.As one main anti-apoptic and enhancing survival pathway in cells, it plays an important role in cellular growth (increased cell size), proliferation (increased cell number), apoptosis, cell survival and migration.At the same time,the pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration disease, epilepsy.In recent years,many studies have shown that the dysfunction of PI3K/Akt/mTOR signaling pathway can lead to neurodevelopmental disease.Loss of tuberous sclerosis complex (TSC)1/2 or phosphatase ad tensin homologue deleted on chromosome 10 (PTEN), or environmental stimuli such as inflammation, epilepsy, or hypoxia may stimulate mTOR-dependent protein synthesis,resulting in a host of cellular, structural, and physiological responses that culminate in clinical symptoms.Study the role of mTOR signaling pathway in early-onset epileptic encephalopathy, discuss the intervention and therapy in early-onset epileptic encephalopathy have important clinical meanings.In this article, the components, physiological functions,information were elucidated relative to the PI3 K/Akt/mTOR signaling pathway, and the interaction of the signaling pathway and epilepsy was discussed.

Objective To compare the recurrence rate and long-term follow-up angiographic findings between stent-assisted coil embolization and simple coil embolization in treating large and giant intracranial aneurysms.Methods The clinical data and imaging materials of a total of 90 patients with large and giant intracranial aneurysms (＞10 mm,91 aneurysms in total),who were admitted to authors' hospital during the period from January 2004 to January 2016 to receive interventional embolization therapy,were retrospectively analyzed.Of the 90 patients,52 patients (52 lesions in total) received simple coil embolization (SCE group)and 38 patients (39 lesions in total) received stent-assisted coil embolization (SACE group).Postoperative recurrence rates of aneurysm were compared between the two groups,and recurrence risk factors were analyzed.Results The whole postoperative recurrence rate of aneurysm and re-treatment rate were 38.5％(35/91) and 20.9％(19/91) respectively;the recurrence rate and re-treatment rate of SACE group were 35.9％ (14/39) and 17.9％ (7/39) respectively,while those of SCE group were 40.4％ (21/52) and 23.1％ (12/52) respectively;the differences between the two groups were not statistically significant (P＞0.05).Multivariate logistic regression indicated that the recurrence risk factors of large or giant intracranial aneurysms included rupture of aneurysm (OR=0.284,95％CI=0.083-0.978,P=0.046),simple coil embolization (OR=5.03,95％ CI=1.04-24.44,P=0.045),concurrent hypertension (OR =0.13,95％ CI=0.036-0.51,P=0.003)and long time after operation (OR=1.002,95％CI=1.001-1.003,P=0.002).Conclusion Compared with simple coil embolization,stent-assisted coil embolization can reduce the recurrence rate of aneurysm.Rupture of aneurysm,simple coil embolization,long time after operation and concurrent hypertension are independent risk factors for recurrence of aneurysm after transcatheter arterial embolization.

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Objective:To analyze the data of vision acuity from primary and secondary school students in different regions in China in a screening program performed by Huaxia Eye Hospital, and to investigate the prevalence and incidence of myopia among them.Methods:A cross-sectional study was conducted.Cross-sectional and cohort analysis of the visual acuity and refraction data of primary and secondary school students in China from 2019 to 2021 from Huaxia Eye Hospital was carried out.Myopia was defined as one eye with the uncorrected visual acuity less than 5.0 and a spherical equivalent <-0.50 D in the screening.The frequency of screening, the number of people, the distribution of vision acuity, and the distribution of myopia among subjects were compared by sexes, grades and regions, and the prevalence and incidence of myopia was analyzed.Standard logarithmic visual acuity chart was used for visual examination and automatic computerized optometry was used for refractive examination.Screening process was consistent in the study.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2019-011). The written informed consent was obtained from subjects or their guardians after explaining the examination procedure, methods and purpose prior to any medical examination.Results:A total of 4 027 schools in 51 cities of 19 provinces covering 4.556 million people were included in the vision study.The prevalence of myopia in screening was 64.85% in primary and secondary school population generally, 54.0% in primary school, 78.18% in junior high school and 87.05% in senior high school.There were statistical differences in the prevalence of screening myopia in different education stages ( χ2=100.7, P<0.001). The prevalence rate in females was higher than that in males ( χ2=5 557.5, P<0.001). The incidence of myopia within a year was 18.68% in primary and secondary schools, which was 16.57% in East China, 6.07% in Central China and North China, 15.11% in Southwest and Northwest China, 9.19% in South China, and there was a statistically significant differences among them ( χ2=1 200.9, P<0.001). Conclusions:The prevalence and incidence of myopia in primary and secondary school students are still high and vary with educational stages and regional factors.Scientific prevention and control of myopia should consider the two factors.

Objective: To explore the impact of Hedgehog protein on human retinal microvascular endothelial cell(HRMEC)and its signaling pathway. Methods: The cultured HRMECs were divided into normal control group, 0.5 μmol/L agonist group and 1.0 μmol/L agonist group, and were cultured in medium with final concentration of 0, 0.5 and 1.0 μmol/L Hedgehog agonist, respectively; HRMECs cultured in high glucose medium were divided into high glucose control group, 1.5 μmol/L inhibitor group and 2.5 μmol/L inhibitor group.Erismodegib, the Smoothed inhibitor with final concentration of 0, 1.5 and 2.5 μmol/L was added into corresponding group, respectively.MTS method and Transwell cell migration method were used to detect the proliferation(A₄₉₀ value)and relative mobility of HRMEC.The phosphorylation of PLCγ1, Akt and Erk proteins were detected by Western blot. Results: The relative expression of Hedgehog protein in the high glucose control group was 6.24±0.11, which was significantly higher than 1.00±0.00 in the normal control group(t=667.573, P<0.001). The A₄₉₀ value was 1.349±0.050 and 1.422±0.053, and the relative mobility rate was 2.34±0.14 and 3.59±0.32 in the0.5 μmol/L agonist group and the 1.0 μmol/L agonist group, respectively, which were significantly higher than 1.203±0.101 and 1.00±0.00 in the normal control group(all at P<0.01). The A₄₉₀ value was 0.849±0.010 and 0.737±0.030, and the relative mobility rate was 0.43±0.02 and 0.27 ±0.01 in the 1.5 μmol/L inhibitor group and the 2.5 μmol/L inhibitor group, respectively, which were significantly lower than 1.000±0.040 and 1.00±0.00 in the high glucose control group(all at P<0.01). The phosphorylation ratios of PLCγ1, Akt and Erk in the 0.5 μmol/L agonist group and the 1.0 μmol/L agonist group were significantly higher than those in the normal control group(all at P<0.01). The phosphorylation ratios of PLCγ1, Akt and Erk in the 1.5 μmol/L inhibitor group and the 2.5 μmol/L inhibitor group were significantly lower than those in the high glucose control group(all at P<0.01). Conclusions High glucose induces the expression of Hedgehog protein in HRMEC.Hedgehog protein may regulate the function of HRMEC by regulating the phosphorylation of PLCγ1, Akt and Erk in G Protein-coupled receptors pathway.

Objective: To investigate the significance of endoplasmic reticulum stress-associated gene tri-bbles pseudokinase 3 (TRIB3) in the long-term brain injury in rats with developing epilepy. Methods: Thirty male SD rats aged 21 days were randomly divided into the control group and the epilepsy group, 15 rats in each group.The rats in the epilepsy group were intraperitoneally injected with kainic acid (10 mg/kg) to induce seizures, while the rats in the control group were injected with the equal volume of 9 g/L saline.The rats in two groups were euthanized at 30 d after kainic acid administration.The damage to the ultrastructure of the cortex were observed by using transmission electron microscopy.Neuronal apoptosis in the cortex of rats was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.The expression and localization of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), TRIB3, and the activation of protein kinase B (AKT) in the cortex were examined by using Western blot analysis and immunohistochemistry. Results: Compared with the control group, the different ultrastructural changes were observed in the cortex in the epilepsy group rats.TUNEL assay indicated that the number of apoptosis cells of cortex in the epilepsy group was increased.The protein levels of GRP78 and TRIB3 were upregulated in the cortex of the epileptic rats (1.280±0.272, 1.725±0.570), compared with the control group (1.000±0.000, 1.000±0.000), and the differences were statistically significant (all P<0.05). There was no significant change in CHOP protein between the control group and the epilepsy group.The level of phosphorylated AKT(p-AKT) was decreased in the cortex of the epilepsy group (0.150±0.047), compared with the control group (1.000±0.000), and the difference was statistically significant (P<0.05). Conclusions The brain injury caused by epilepsy in the developing rats can sustain to the stage of mature rats, and the endoplasmic reti-culum stress-associated gene TRIB3 is involved in the pathogenesis of long-term brain damage in the rats with deve-loping epilepsy.

Objective:To compare the effects of different intraocular infusion solutions on histology and function of retina.Methods:Human corneal endothelial cells (HCEC), human retinal pigment epithelium (HRPE) cells and rat retinal ganglion cells (RGC) were divided into normal control group, balanced saline solution (BSS) group and compound electrolyte intraocular irrigating solution (CEIIS) group, and the cells were cultured in 10% DMEM/F12 medium, BSS and CEIIS for 12, 24 and 48 hours, respectively, according to grouping.The proliferation absorbance value of cultured cells was measured by cell counting kit-8 (CCK8) method.The expression of apoptosis related proteins in cultured cells was detected by cellular immunofluorescence staining.The cell apoptosis rate and cell cycle were measured by flow cytometry.The mitochondrial damage was detected by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) quantitative detection kit.Fifteen New Zealand white rabbits were randomly divided into control group ( n=3), BSS group ( n=6) and CEIIS group ( n=6). The left eyes were taken for vitrectomy and different intraocular perfusion fluids were used during vitrectomy according to grouping.The retinal function of operative eyes was measured by flash electroretinogram (ERG) before operation and 24 hours after operation, and the structural changes of each layer of retina were detected by optical coherence tomography (OCT). The early apoptosis of retinal cells was detected by TUNEL staining.The expressions of cytochrome C and bax protein in retina were detected by immunohistochemical staining.The ultrastructural changes of retina were observed under a transmission electron microscope.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Peking University People's Hospital (No.2019PHE059). Results:The three kinds of cultured cells in BSS and CEIIS groups were damaged in various degrees.With the extension of culture time, proliferated cells were decreased and the number of apoptotic cells was increased.Compared with the BSS group, cultured cells in the CEIIS group were dense and in orderly arrangement with uniform morphology and size.The apoptosis rates of HRPE cells and RGC in the BSS group were (37.157±6.918)% and (29.993±12.330)%, respectively, which were significantly higher than (4.163±1.310)% and (6.337±1.903)% in the CEIIS group ( P=0.003, 0.045). There was no significant difference in G0/G1+ S phase ratio of HCEC and HRPE cells among the normal control group, BSS group and CEIIS group (HCEC: F=2.226, P=0.189; HRPE: F=2.634, P=0.151), and the proportion of G2/M division arrest phase of RGC in the BSS group was significantly higher than that in the normal control group and CEIIS group ( P=0.047, 0.024). The proliferation absorbance values of HCEC, HRPE cells and RGC in the CEIIS group were significantly higher than those in the BSS group at each culture time point (all at P<0.05). The fluorescence intensity of cytochrome C, bax, caspase-3 and caspase-9 proteins in the BSS group was stronger than that in the normal control group and CEIIS group, and the fluorescence intensity of bcl-2 was weaker than that in the CEIIS group, and the fluorescence intensity of zonula occluden-1 (ZO-1) was weaker than that in the normal control group and CEIIS group.The release level of LDH in the BSS group was significantly higher than that in the CEIIS group at different time points (all at P<0.001). After 48 hours of culture, the release level of SDH in the BSS group was significantly higher than that in the CEIIS group ( P<0.05). No retinal histological abnormalities was found through OCT examination of rabbit eyes after vitrectomy in the two groups, but transmission electron microscopy showed that there were different degrees of loose arrangement of retinal photoreceptor cells, a large number of photoreceptor outer membrane discs falling off and vacuolar degeneration in the two groups, especially in the BSS group.TUNEL staining showed that the apoptotic cells were mainly located in the inner nuclear layer and RGC layer.The number of apoptotic retinal cells was (135.2±22.8)/high-power field of vision in the BSS group, which was significantly higher than (81.3±17.7)/high-power field of vision in the CEIIS group ( t=4.175, P=0.002). Full field flash ERG showed that the amplitudes of scotopic 3.0 ERG a- and b-wave in the CEIIS group after operation were significantly lower than those before operation, but the differences were not statistically significant (all at P>0.05). The amplitudes of scotopic 3.0 ERG a- and b-wave in the BSS group after operation were significantly lower than those before operation ( P=0.026, 0.010). Conclusions:In vivo and in vitro research results show that compared with BSS, there were few apoptotic cells in retinal tissue after vitrectomy perfused by CEIIS.