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Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

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AIM: To identify immune-related key genes and the extent of immune cell infiltration in a oxygen-induced retinopathy(OIR)model by bioinformatics method.METHODS: Microarray data were obtained from the GEO database, differentially expressed genes(DEGs)were identified using the “limma” R package, GO function enrichment and KEGG pathway analysis were conducted, and immune cell infiltration based on the CIBERSORT algorithm was analyzed. Weighted gene co-expression network analysis(WGCNA)was used to screen DEGs in the immune-related gene module, constructing a protein-protein interaction(PPI)network using STRING online database and Cytoscape software, and further screening final target genes using the cytoHubba plug-in.RESULTS: A total of 467 DEGs were screened, including 270 up-regulated and 197 down-regulated genes. Helper T cell 2(Th2 cells), an immune cell type, exhibited significantly high expression levels(P<0.05). WGCNA analysis identified 66 differential genes in modules most closely related to immunity. After constructing the PPI network, 5 key genes were screened through plug-ins: von Willebrand factor(vWF), vascular endothelial growth factor A(VEGF-A), Serping1, apoptosis inducing factor 1(AIF1)and signal transducers and activators of transcription 3(STAT3).CONCLUSION: The findings of this study provide valuable insights into immune cell infiltration in OIR as well as key genes related to immunity through bioinformatics analysis, which can serve as a reference for further research and treatment of retinal neovascular diseases.

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Objective:To investigate the clinical efficacy of triamcinolone acetonide peribulbar injection combined with vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment (RRD-CD).Methods:This study was a retrospective case series study. Nineteen cases (19 eyes) with RRD-CD who had undergone pars plana vitrectomy at the Dalian No.3 People′s Hospital were analyzed. All the cases received 20 mg triamcinolone acetonide peribulbar injection within 3 to 7 days before surgery. The severity of patient′s uveitis was assessed before and after peribulbar injection of triamcinolone acetonide. Best corrected visual acuity (BCVA) and intra ocular pressure (IOP) before and after surgery, the area of retinal detachment, the rate of retinal reattachment, the rate of recurrent retinal detachment and surgical complications were analyzed. Patients′ blood pressure and blood glucose levels were also monitored.Results:19 patients were followed up for (13.1±1.5)months. The severity of uveitis reduced to different extents compared with preoperative condition. The IOP was (8.73±3.38)mmHg before injection and (10.95±2.46)mmHg after injection, and the difference was statistically significant ( t=-7.571, P=0.027). The choroid detachment range was 4-12(9.37±2.69)sites before injection, and 0-11(4.63±4.10)sites after injection, and the difference was statistically significant ( Z=-3.834, P=0.001). Compared with the preoperative results, the BCVA increased in 12 patients, unchanged in 5 cases and decreased in 2 cases. In the final follow-up of 18 patients with retinal reattachment, 17 eyes underwent a single operation, 2 eyes had recurrent retinal detachment, and 1 eye had retinal reattachment after a second operation. There were no significant difference in blood glucose and blood pressure before and after injection (all P>0.05). There were no other complications besides temporarily elevated IOP and cataract. Conclusions:Vitrectomy combined with triamcinolone acetonide peribulbar injection is effective and safe for patients with RRD-CD.

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Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

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Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

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Objective To investigate the effects of sevoflurane post-conditioning on oxidative stress and inflammatory reaction during rat cerebral ischemia-reperfusion, and to explore its cerebral protective mechanism.Methods Thirty-six health male Sprague-Dawley rats (aged 12-14 weeks, weighing 220-260 g) were randomly divided into 3 groups (n=12 each): sham control group (group Sham), cerebral ischemia-reperfusion group (group IR), sevoflurane post-conditioning group (group SPC).Cerebral ischemia-reperfusion model was established, ischemia for 30 min followed by reperfusion 24 h.Rat middle cerebral artery was not occluded in group Sham.Cerebral ischemia-reperfusion model was established in group IR.Group SPC was subjected to 2.6% sevoflurane for 15 min in the beginning of reperfusion.At the end of reperfusion, rats were cut off the head to take out the brain tissue.The expression level of Iba-1 and HO-1 proteins was measured by western blot.The levels of reactive oxygen species (ROS), malondialdehyde (MDA), TNF-α, IL-1β and the activity of superoxide dismutase (SOD) were evaluated.Results Compared with group Sham, the expression of cerebral cortex Iba-1 protein was higher than that in groups IR and SPC (P＜0.05), the expression of Iba-1 protein in group SPC was lower than that in group IR (P＜0.05).Compared with group Sham, the contents of ROS, MDA, TNF-α and IL-1β were increased in groups IR and SPC (P＜0.05), but the activity of SOD and expression of HO-1 protein were decreased (P＜0.05).And the contents of ROS, MDA, TNF-α and IL-1β in group SPC were less than those in group IR, the activity of SOD and expression of HO-1 protein in group SPC were higher than those in group IR.Conclusion Sevoflurane post-conditioning can mitigate the microglia activation, reduce cerebral oxidative stress and inflammation, thus protect rat cerebral against ischemia reperfusion injury.

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Objective: To investigate the effect of sevolfurane (SEVO) post-conditioning on protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway for protecting ischemia/reperfusion (I/R) injury in isolated rat’s heart. Methods: A total of 84 isolated rat’s heart prepared by Langendorff method were randomly divided into 7 groups andn=12 in each group.①Sham group,②I/R group,③SEVO post- conditioning (SPC) group,④NVP-BEZ235 solvent dimenthyl sulfoxide (DMSO) group,⑤Phosphatidyl inositol 3-kinase (PI3K)/mTOR dual inhibitor NVP-BEZ235 (BEZ) group,⑥BEZ+SPC group and⑦SEVO alone group. The hearts received 30 min ischemia followed by 120 min reperfusion with relevant treatment except for Sham group and SEVO group in which the hearts were without ischemia process. Myocardial infarct (MI) size and tissue pathological changes were observed, protein expressions of phosphor-AKT (P-AKT)/total-AKT, P-mTOR/total-mTOR, Beclin1, Bax/Bcl-2 and cleaved Caspase-3 were examined at the end of reperfusion respectively. Results: Compared with I/R group, SPC group presented decreased MI size (26.28±4.00) % vs (49.22±3.66) % and reduced tissue pathological changes; up-regulated protein expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 79.85% and 67.02%, while down-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 33.77%, 69.26% and 48.84%respectively, allP<0.05. Compared with SPC group, BEZ+SPC group sowed increased MI size (53.85±4.06) % vs (26.28±4.00) %and elevated tissue pathological changes; down-regulated proteins expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 46.06% and 42.95%, while up-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 29.90%, 206.85% and 114.65% respectively, allP<0.05. Conclusion: SPC may activate AKT/mTOR pathway and inhibit cardiomyocyte autophagy and apoptosis, thereby attenuate I/R injury in isolated rats’ heart.

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Objective To study the inhibitory effects of andrographis paniculata and silybum marianum on the efflux system of MRSA 41577. Methods Inhibitory effects of andrographis paniculata and silybum marianum on efflux system of MRSA 41577 was evaluated using fluorescence spectrophotometry.PCR was applied to detect the norA efflux gene.By RT-PCR method for detection of andrographis paniculata and silybum marianum influence of the expression of norA efflux gene.Results Andrographis paniculata and silybum marianum significantly increased the accumulation of ciprofloxacin in MRSA 41577 in a time-dependent manner.At 12 minute, andrographis paniculata and silybum marianum respectively increased ciprofloxacin in MRSA41577 by 49% and 76%( P <0.05 ) , which is superior to that of reserpine. Further mechanism studies indicated that andrographis paniculata and silybum marianumcould reduce the expression of norA in MRSA 41577.After incubated with andrographis paniculata and silybum marianum for 16 h, the relative expression of norA of MRSA41577 was respectively reduced by 35% and 42% ( P <0.05 ). Conclusion Andrographis paniculata and silybum marianumcould inhibit MRSA efflux system through reducing pathogen ’s expression of norA and NorA protein.

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Objective To investigate the role of AKT/GSK3β/mTOR signaling molecule in myocardial protection of sevoflurane postconditioning.Methods Thirty-nine male Sprague-Dawley rats,weighing 200-250 g,installed in vivo myocardial ischemia-reperfusion model by left anterior de-scending coronary occlusion for 30 min.Rat hearts were randomly divided into 3 groups (n = 13 ):sham control group (group Sham),purely ischemia-reperfusion group (group IR),sevoflurane post-conditioning group (group SPC).With the exception of group Sham,each group was subjected to oc-clusion for 30 min followed by 2 h reperfusion.Group SPC was subjected to sevoflurane postcondi-tioning:2.4% sevoflurane was inhaled for 1 5 min starting from the end of ischemia until 1 5 min after beginning of reperfusion,while 33% oxygen was inhaled in the other groups.At the end of 2 h reper-fusion,cardiac function was evaluated by two-dimensional echocardiography,myocardial infarction size was measured by using 1% 2,3,5-triphenyltetrazolium chloride triazole (TTC),myocardial ultra-structural alterations was detected by transmission electron microscopy (TEM),cardiomyocytes ap-optosis was examined by terminal deoxynucleotidyl nickend labeling (TUNEL),the expressions of p-AKT/t-AKT, p-GSK3β/t-GSK3β, p-mTOR/t-mTOR,Bcl-2 and Bax proteins was measured by Western blot.Results Compared with group Sham,cardiac function was deteriorated,myocardial in-farct size was increased,cardiomyocyte mitochondrial damage was increased,positive apoptotic car-diomyocyte was increased,the expression of Bcl-2 was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bax were up-regluated in group IR (P <0.05).Compared with group IR,cardiac function was improved,myocardial infarct size was de-creased,cardiomyocyte mitochondrial damage was decreased,positive apoptotic cardiomyocyte was decreased,the expression of Bax was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bcl-2 were up-regluated in group SPC (P < 0.05 ). Conclusion Sevoflurane postconditioning can mitigate ischemia-reperfusion injury to in vivo rat hearts,decreased cardiomyocyte mitochondrial damage,inhibited cardiomyocyte apoptosis,and its mechanism was related to the activation of AKT/GSK3β/mTOR signaling molecule.