The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

Extracellular vesicles(EVs)are small vesicles secreted by cells,widely present in various body fluids,and they play important biological roles.In recent years,EVs have garnered significant attention as novel diagnostic and thera-peutic tools in multiple ocular diseases.Glaucoma,as a common cause of irreversible blindness,is primarily caused by optic nerve damage associated with pathologically elevated intraocular pressure.Emerging evidence indicates that EVs hold considerable therapeutic potential in glaucoma management,particularly in modulating aqueous humor circulation and pro-viding retinal neuroprotection.This review summarizes the latest research progress on EVs in the treatment of glaucoma.

With the increasing emphasis on patient-centered care and psychosocial support in modern healthcare systems,the role of medical social workers has evolved from auxiliary support to comprehensive participation.They serve as crucial liaisons for the healthcare service,delivering humanistic care for patients.Specially,their service has extended beyond traditional psycho-social counseling and doctor-patient communication to encompass whole-course care,community resource coordination,and pa-tient empowerment across multiple domains.As policies promoting humanistic healthcare and holistic well-being are progressively implemented,the scope of work for medical social workers has deepened and broadened in terms of role positioning and service demands.However,they also encounter significant challenges,including role ambiguity,interprofessional collaboration barriers,and insufficient institutional support mechanisms.To address these challenges,enhanced interprofessional education,evidence-based practice implementation,and policy-driven mechanisms are essential for strengthening their clinical competencies,delinea-ting professional boundaries,and optimizing resource allocation.These synergistic approaches collectively reinforce medical social workers'integral role in advancing humanistic care models while elevating their professional stature within the evolving healthcare ecosystem.

Glaucoma,characterized by optic nerve damage and progressive damage to retinal ganglion cells(RGCs),is the leading cause of irreversible blindness.However,the specific mechanism of RGC damage has not been fully elucida-ted.In recent years,there is increasing evidence that microglia,especially disease-associated microglia(DAM),may play an important role in glaucomatous ganglion cell injury.In this paper,we reviewed the role and mechanism of DAM in RGC damage in glaucoma,aiming to provide new insights for further research on the mechanism of RGC damage and subsequent protection of RGCs.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Objective To investigate the effects of DNA Cross-Link Repair 1A(DCLRE1A)on mitochondrial func-tion in lens epithelial cells(LECs).Methods Thirty eyes from 30 patients with age-related cataracts(ARC)were select-ed and divided into three groups:cortical type(ARCC group),nuclear type(ARNC group),and posterior subcapsular type(ARPC group),with 10 cases in each group.Additionally,10 eyes from 10 age-matched patients diagnosed with epiretinal membrane and having clear lenses were selected as the control group.Western blot was used to detect the ex-pression levels of DCLRE1A protein in the anterior capsule tissues of patients in each group and in the lens epithelial cell line(SRA01/04)treated with hydrogen peroxide(H2O2)in vitro and overexpressed DCLRE1A model(OE-DCLRE1A group).The effects of overexpressed DCLRE1A on the expression levels of mitochondrial transcription factor(TFAM)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC1α)proteins were also detected.Normal cultured SRA01/04 cells were randomly divided into Control group(untreated),H2 O2 group,H2 O2+HA group(transfected with control plasmid HA),and H2O2+OE-DCLRE1A group(transfected with DCLRE1A plasmid).RT-PCR was used to measure mtD-NA expression in each group cells.Changes in mitochondrial membrane potential(MMP)and mitochondrial reactive oxy-gen species(ROS)in each group were detected by immunofluorescence staining.Results Western blot analysis showed that compared with the control group cells,the relative expression levels of DCLRE1A protein in the anterior capsule tis-sues of patients in the ARCC,ARNC,and ARPC groups were all decreased,with statistically significant differences(all P＜0.001).In the in vitro H2O2-induced oxidative damage model,compared with the Control group,the relative expression level of DCLRE1A protein in the H2O2 group was significantly decreased(P＜0.001).The overexpression efficiency results of DCLRE1A showed that,compared with the Control group,the relative expression level of DCLRE1A protein in the OE-DCLRE1A group cells was significantly increased,with statistical significance(P＜0.001).RT-PCR results showed that compared with the H2O2+HA group,the expression level of mtDNA in the H2O2+OE-DCLRE1A group was significantly in-creased(P＜0.001).Western blot analysis showed that compared with the H2O2+HA group,the relative expression levels of TFAM and PGC1α proteins in the H2O2+OE-DCLRE1A group were significantly increased(P＜0.001).Immunofluores-cence staining results showed that compared with the H2O2+HA group,the MMP level in the H2O2+OE-DCLRE1A group was significantly restored,and the accumulation of mitochondrial ROS was reduced(P＜0.001).Conclusion Under H2O2-induced oxidative stress conditions,DCLRE1A promotes the repair of damaged mtDNA in LECs by regulating mito-chondrial biogenesis,thereby reducing LEC apoptosis and participating in the occurrence and development of ARC.

Glaucoma,characterized by optic nerve damage and progressive damage to retinal ganglion cells(RGCs),is the leading cause of irreversible blindness.However,the specific mechanism of RGC damage has not been fully elucida-ted.In recent years,there is increasing evidence that microglia,especially disease-associated microglia(DAM),may play an important role in glaucomatous ganglion cell injury.In this paper,we reviewed the role and mechanism of DAM in RGC damage in glaucoma,aiming to provide new insights for further research on the mechanism of RGC damage and subsequent protection of RGCs.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Objective To investigate the effects of DNA Cross-Link Repair 1A(DCLRE1A)on mitochondrial func-tion in lens epithelial cells(LECs).Methods Thirty eyes from 30 patients with age-related cataracts(ARC)were select-ed and divided into three groups:cortical type(ARCC group),nuclear type(ARNC group),and posterior subcapsular type(ARPC group),with 10 cases in each group.Additionally,10 eyes from 10 age-matched patients diagnosed with epiretinal membrane and having clear lenses were selected as the control group.Western blot was used to detect the ex-pression levels of DCLRE1A protein in the anterior capsule tissues of patients in each group and in the lens epithelial cell line(SRA01/04)treated with hydrogen peroxide(H2O2)in vitro and overexpressed DCLRE1A model(OE-DCLRE1A group).The effects of overexpressed DCLRE1A on the expression levels of mitochondrial transcription factor(TFAM)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC1α)proteins were also detected.Normal cultured SRA01/04 cells were randomly divided into Control group(untreated),H2 O2 group,H2 O2+HA group(transfected with control plasmid HA),and H2O2+OE-DCLRE1A group(transfected with DCLRE1A plasmid).RT-PCR was used to measure mtD-NA expression in each group cells.Changes in mitochondrial membrane potential(MMP)and mitochondrial reactive oxy-gen species(ROS)in each group were detected by immunofluorescence staining.Results Western blot analysis showed that compared with the control group cells,the relative expression levels of DCLRE1A protein in the anterior capsule tis-sues of patients in the ARCC,ARNC,and ARPC groups were all decreased,with statistically significant differences(all P＜0.001).In the in vitro H2O2-induced oxidative damage model,compared with the Control group,the relative expression level of DCLRE1A protein in the H2O2 group was significantly decreased(P＜0.001).The overexpression efficiency results of DCLRE1A showed that,compared with the Control group,the relative expression level of DCLRE1A protein in the OE-DCLRE1A group cells was significantly increased,with statistical significance(P＜0.001).RT-PCR results showed that compared with the H2O2+HA group,the expression level of mtDNA in the H2O2+OE-DCLRE1A group was significantly in-creased(P＜0.001).Western blot analysis showed that compared with the H2O2+HA group,the relative expression levels of TFAM and PGC1α proteins in the H2O2+OE-DCLRE1A group were significantly increased(P＜0.001).Immunofluores-cence staining results showed that compared with the H2O2+HA group,the MMP level in the H2O2+OE-DCLRE1A group was significantly restored,and the accumulation of mitochondrial ROS was reduced(P＜0.001).Conclusion Under H2O2-induced oxidative stress conditions,DCLRE1A promotes the repair of damaged mtDNA in LECs by regulating mito-chondrial biogenesis,thereby reducing LEC apoptosis and participating in the occurrence and development of ARC.

With the increasing emphasis on patient-centered care and psychosocial support in modern healthcare systems,the role of medical social workers has evolved from auxiliary support to comprehensive participation.They serve as crucial liaisons for the healthcare service,delivering humanistic care for patients.Specially,their service has extended beyond traditional psycho-social counseling and doctor-patient communication to encompass whole-course care,community resource coordination,and pa-tient empowerment across multiple domains.As policies promoting humanistic healthcare and holistic well-being are progressively implemented,the scope of work for medical social workers has deepened and broadened in terms of role positioning and service demands.However,they also encounter significant challenges,including role ambiguity,interprofessional collaboration barriers,and insufficient institutional support mechanisms.To address these challenges,enhanced interprofessional education,evidence-based practice implementation,and policy-driven mechanisms are essential for strengthening their clinical competencies,delinea-ting professional boundaries,and optimizing resource allocation.These synergistic approaches collectively reinforce medical social workers'integral role in advancing humanistic care models while elevating their professional stature within the evolving healthcare ecosystem.