Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.

Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.

Objective To discuss the pathogenesis of postmenopausal osteoporosis,and to validate molecular docking and predict the composition of traditional Chinese medicine based on reverse network pharmacological.Methods The shared targets of"osteoporosis"and"postmenopausal"were extracted and demonstrated by using Venn diagram.The common targets were analyzed for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.The protein-protein interaction(PPI)network was constructed to clarify the pathogenesis,pathways and key targets of postmenopausal osteoporosis,and finally the key target-active ingredient-traditional Chinese medicine network was constructed,and the characteristics,taste and tropism of traditional Chinese medicines with high identification values were sorted out.Results For postmenopausal osteoporosis,17 key targets of which degree value ≥ 10 that could match with traditional Chinese medicines were analysis in traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the results of 18 times of molecular docking tests were stable and good which performed on the highest degree value 3 targets with 6 traditional Chinese medicines components(degree value≥5,oral bioavailability≥30％,drug likeness≥0.18).Collected 52 kinds of traditional Chinese medicines(degree value ≥4)were mainly cold and bitter,belonging to liver and lung channels in channel tropism,promoting blood circulation and removing blood stasis in efficacy from 300 kinds of traditional Chinese medicines.Conclusion In this study,the targets,pathways,compositions and prescriptions were predicted for postmenopausal osteoporosis based on reverse network pharmacological and molecular docking.However,the thinking be broadening for the formulation of traditional Chinese medicine which appropriately added bitter cold drugs、drugs entering liver and lung channels,blood-activating and blood-stasis removing drugs and high-value Chinese medicines such as Ginkgo biloba,Cuscuta,Cauleratholoba,Licorice and Astragalus to improve joint inflammation,inhibit osteoclast differentiation,promote osteoblast differentiation and prevent osteoporosis for the treatment of postmenopausal osteoporosis.

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype