AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Angiopoietin-like protein (ANGPTL), a group of secreted glycoproteins, is widely expressed in vivo and is involved in many pathophysiological processes such as glycolipid metabolism, stem cell growth, local inflammation, vascular leakage and angiogenesis. Many kinds of ANGPTL are closely related to the occurrence and development of diabetic retinopathy (DR), especially ANGPTL4, which has gradually become a new hotspot in the field of DR Research. ANGPTL is involved in glucose metabolism and lipid metabolism, promotes increased vascular permeability, pathological angiogenesis, and participates in intraocular inflammation. ANGPTL is a promising molecular target. It can not only be used as a biomarker to predict the occurrence and progression of DR, but also provide new ideas for the treatment of DR by making antibody drugs to interfere with this molecule.

Objective: To investigate the inhibitory effect of polydopamine (PDA) on enamel demineralization in isolated teeth and the induction of hydroxyapatite (HA) production on the surface of demineralized enamel to provide a novel protocol for the prevention and treatment of enamel demineralization. Methods: Twenty isolated bovine teeth were cut into 20 enamel slices and randomly divided into an experimental group and a control group, with 10 slices in each group. The enamel slices in the experimental group were immersed in 2 mg/mL freshly prepared dopamine solution and incubated for 24 hours at room temperature in the dark to prepare the PDA coating, while the control group was left untreated. Then, the isolated bovine teeth, with and without PDA coating, were immersed in artificial demineralization solution at 37 °C for 3 days, followed by 7 days in simulated body fluid (SBF), and the immersion solution was changed daily. The surface morphology of enamel was observed by scanning electron microscopy (SEM), the calcium/phosphorus ratio of the enamel surface was analyzed by energy dispersive spectroscopy (EDS), and the characteristic functional groups in enamel deposits were analyzed by Fourier transform infrared spectroscopy (FTIR). Results: Compared with the control group, the number of demineralized pores produced after 3 d of enamel demineralization with polydopamine coating was less, and the diameter was smaller. EDS elemental analysis showed that the Ca/P ratio after enamel demineralization was 2.37 in the experimental group, which was smaller than the 2.53 ratio in the control group. In the remineralization experiment, after 7 days of remineralization of PDA coated enamel in the experimental group, lamellar grains were produced on the enamel surface, and the growth showed obvious directionality, growth regularity and uniform arrangement. In the control group, the surface of enamel was flocculent mineral deposit, and the crystallinity was poor. The FTIR results proved that the enamel surface deposit of PDA-coated enamel was HA after 7 d of remineralization. Conclusion PDA can affect the nucleation process of HA and promote the production of HA on the surface of demineralized enamel.

Objective: To observe the clinical efficacy of minimally invasive vitreous surgery (MIVS) for special rhegmatogenous retinal detachment (RRD) in children and adolescents. Methods: A retrospective clinical comparative study. Fourteen eyes with special type of RRD in 14 children and adolescents who received the MIVS treatment from January 2014 to January 2019 in Ophthalmology Department of The First Affiliated Hospital Ophthalmology of Air Force Military Medical University, were included in this study. Among them, 8 eyes from 8 males and 6 eyes from 6 females. The age of them ranged from 5 to 17, with the mean age of 12.64±4.11 years. The course of disease was ranged from 1 d to 1 year, and the average of it was 30 d. All the eyes developed the special type RRD, including pseudophakic and aphakic retinal detachment, giant retinal tear with retinal detachment, choroidal detachment associated with retinal detachment, and RRD with ocular dysplasia. In the 14 eyes, there was 2 eyes with retinal detachment in 1 quadrant, 4 eyes in 2 quadrants, 1 eye in 3 quadrants and 7 eyes in total 4 quadrants. All the eyes were treated with 23G or 25G MIVS and filled with irrigation solution, air and silicone oil. In addition, 10.4 months' follow-up for average after surgery were taken to observe the occurrence of retinal reattachment, BCVA and related complications in the eyes. Results: In the 14 eyes, 13 (92.9%) of them attained retinal reattachment and 1 eye (7.1%) got a poor retinal reattachment after one operation. At the last follow-up, all the 14 eyes (100.0%) attained retinal reattachment and 5 of them at the filling state of silicone oil. The vision of 8 eyes (57.1%) were improved, 4 eyes (28.6%) have no notable changes and 2 eyes decreased (14.3%). During the operation, iatrogenic retinal breaks were occurred in 1 eye, and silicone oil entered underneath the retina in 1 eye. After the operation, 1 eye suffered a relapse of retinal detachment after the removal of silicone oil and then were filled with it again. Conclusions MIVS is a safe and effective way to treat the special type RRD among the children and adolescents. The rate of retinal reattachment is 92.9% after one surgery and 100.0% at the last follow-up. Therefore, MIVS can help most of eyes with special type RRD to get a stable and improved vision.

Objective To investigate the values of combined detection of serum pancreas autoantibodies (PAB),anti-saccharomyces cerevisiae antibodies(ASCA),goblet cell autoantibodies(GAB) and antineutrophil cytoplasmic antibodies(PANCA) and fecal calprotectin(FC) in the diagnosis and differential diagnosis of inflammatory bowel diseases(IBD).Methods The serum and feces samples from IBD patients,including 107 with definite Crohn's disease(CD) and 98 with definite ulcerative colitis(UC),and 79 non-IBD patients as the control were collected.Serum PANCA,ASCA,GAB and PAB were detected by an indirect immunofluorescence assay,and FC concentration by double-antibody sandwich ELISA.The results from different patients were compared and analyzed.Results The positive rates of serum PANCA,GAB,PAB and ASCA in 205 IBD patients were 36.1％,29.8％,38.0％ and 4.9％,respectively.The FC concentrations in IBD,CD and UC patients were significantly higher than that in the control(P ＜ 0.01),while there was no statistical difference between CD and UC patients (P ＞ 0.05).The positive rates of PANCA in CD and UC patients were 8.4％ and 66.3％,respectively,while those of PAB in CD and UC patients were 65.4％ and 8.2％,respectively.The sensitivity and specificity of PAB,PANCA,GAB,ASCA,FC and their combination in the differential diagnosis of IBD and non-IBD were 38.0％,36.1％,29.8％,4.9％,54.1％,63.4％ and 98.7％,96.2％,94.9％,100％,68.4％,93.7％,respectively.The area under the ROC of the combination of 5 markers was 0.819 in differentially diagnosing IBD and non-IBD.The area under the ROC of PANCA for the differential diagnosis of UC was 0.816,while that of PAB for the differential diagnosis of CD was 0.823.Conclusion GAB is an autoantibody associated with IBD,which may be helpful for the auxiliary diagnosis of IBD.PAB and PANCA are the important serological markers for the diagnosis of CD and UC,respectively.The combination of FC with PAB,PANCA,GAB and ASCA may be used for the differential diagnosis of IBD and non-IBD,but has little value in distinguishing CD and UC.

Objective To investigate the effect of minocycline on development of diabetic neuropathic pain in rats and its mechanism.Methods Forty male Sprague-Dawley rats aged 6-8 weeks,weighting 180-220 g,were randomly assigned into 4 groups,with 10 rats in each group:normal control group (group C),normal+minocycline group (group C+M),diabetes mellitus group (group DM),diabetes+minocycline group (group DM+M).Diabetes models of rats in group DM and group DM+M were established by single intraperitoneal injection of streptozotocin (STZ,65 mg/kg),and equal volume of normal saline was injected instead of STZ into group C and group C+M;the fasting blood glucose level was tested every week,and the rats of blood glucose level ≥ 16.6 mmol/L were selected otherwise by additional injection of STZ.Two weeks after that,the intervention treatment of rats was given by single intraperitoneal injection ofminocycline (40 mg/kg) in group DM+M and group C+M.The thermal tail flick latency (TFL),thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were detected one day prior to the injection of STZ (T0),and one (T1),2 (T2),4 (T3) and 8 (T4) weeks after the injection of STZ.Eight weeks after that,the expressions of malondialdehyde (MDA) and superoxide dismutase (SOD) in the spinal dorsal ofthe rats were detected by principles ofphysical chemistry with enzyme standard instrument,and apoptotic cells in dorsal hom was detected by immunohistochemistry.Results As compared with those in group C and group C+M,TFL,TWL and MWT in group DM and group DM+M were significantly decreased at T2,T3 and T4 (P＜0.05);TFL,TWL and MWT in group DM+M were significantly increased as compared with those in group DM,reaching their peak levels at T4,with significant differences (P＜0.05).SOD level in group D and group DM was significantly lower than that in group C (P＜0.05),and MDA level in group D and group DM was significantly higher than that in group C (P＜0.05);as compared with group DM,group DM+M had higher SOD level and lower MDA level,with significant differences (P＜0.05).The number of apoptotic cells in spinal dorsal of the rats in group DM was significantly larger than that in group C (P＜0.05).Conclusion Minocycline can relieve diabetic neuropathy pain,and the underlying of mechanisms may be through anti-inflammatory,anti-oxidant stress,anti-apoptosis,and reducing the microglia activation in the spinal cord.