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.

Objective:To investigate the incidence of visual fatigue among military pilots during flights or simulated flights and analyze the correlations among the multidimensional evaluation indicators of visual fatigue.Methods:A total of 172 pilots from an Air Force unit were selected between March 2022 and August 2023. A self-made pilot visual fatigue scale [involving the basic information, visual fatigue status scale (VFSS), and visual quality scale (VQS) was used. The visual fatigue among pilots of different types was compared. Pearson correlation analysis was used to explore the correlations between the cumulative duration of visual display terminal (VDT) and the dimensions of the VFSS, as well as between dimensions of the VFSS and the VQS. Multiple linear regression was used to identify the determinants of the score of the VQS.Results:A total of 172 questionnaires were issued, 146 of which were valid, with an effective rate of 84.88%. Among the 146 military pilots, 73 were fighter pilots and 73 were pilots of other aircraft types (20 bombers, 5 helicopters, 36 transporters, 8 trainers, and 4 fighter-bombers). There were significant differences in the scores of various dimensions and the total score of the VFSS between pilots who were different in age, aircraft types, maximum single-sortie flight durations, and in the proportion of time spent viewing cockpit displays during flight missions ( F=4.93-14.41, t=2.37-4.86, all P<0.01 or <0.05). Significant differences in visual disturbance, systemic symptoms, environmental factors, and the total visual fatigue score were observed between pilots whose total flying hours were different ( F=14.18, 4.90, 4.66, 8.12, P<0.001, =0.009,0.011, <0.001). However, there were no significant differences in the scores of any dimension or in the total score of the VFSS between pilots with a history of ocular trauma or disease and those without (all P>0.05). The cumulative duration of VDT use was positively correlated with the scores of all dimensions and the total score of the VFSS ( r=0.353, 0.303, 0.312, 0.250, 0.356, P<0.001, <0.001, <0.001, =0.002, <0.001), the dimensions of which were positively correlated with those of the VQS ( r=0.448-0.781, all P<0.01). Age ( B=1.524, 95% CI: 0.503-2.545), proportions of time spent viewing cockpit displays during flight missions ( B=3.721, 95% CI: 1.683-5.759), starburst ( B=2.346, 95% CI: 0.516-4.176), blurred vision ( B=3.517, 95% CI: 1.168-5.866), visual fluctuation ( B=2.997, 95% CI: 1.036-4.957) and halo ( B=2.415, 95% CI: 0.469-4.362) were contributors to the total visual fatigue score. Conclusions:The scores of various dimensions and the total score of visual fatigue status in military pilots can increase with age, peak in the group ages 40 to 49, and then decline. Fighter pilots experience lower levels of visual fatigue than those of other aircraft types. The visual quality scale can serve as a reference for assessing pilots′ visual fatigue status. Cumulative durations of VDT use are positively correlated with the degree of visual fatigue. Age, proportions of time spent viewing cockpit displays during flight missions, starburst, blurred vision, visual fluctuation and halo can be used to quickly assess the risk level of visual fatigue among pilots.

Objective:To investigate the interaction of risk factors for diabetic retinopathy (DR) occurrence.Methods:A cross-sectional study was performed.A total of 6 783 diabetic patients with complete survey data from 2005 to 2018 in the National Health and Nutrition Survey database were enrolled, among which 4 426 patients were included according to inclusion criteria and were divided into non-DR diabetes group of 3 491 cases and DR group of 935 cases.The related risk factors were collected, including age, gender, race, residential status, education, annual household income, body mass index (BMI), fasting glucose, glycosylated hemoglobin, duration of diabetes, family history of diabetes, comorbidities, smoke, alcohol use, sleep, physical activity.Patient Health Questionnaire (PHQ-9) was used to assess the psychological status.After the categorization of all variables, risk factors of DR were analyzed by logistic regression, and the interaction between factors was further analyzed.Results:Multivariate analysis showed that female[odds ratio ( OR)=1.33, 95% confidence interval ( CI): 1.02-1.72], duration of diabetes ≥10 years ( OR=1.03, 95% CI: 1.02-1.04), insulin therapy ( OR=2.38, 95% CI: 1.87-3.05), urinary albumin creatinine ratio (UACR) ≥30 mg/g ( OR=1.55, 95% CI: 1.22-1.96) and depression ( OR=1.44, 95% CI: 1.13-1.83) were risk factors for DR, and BMI≤28 kg/m 2 ( OR=0.70, 95% CI: 0.55-0.89) was a protective factor for DR.Furthermore, interaction analysis revealed additive interaction between UACR ≥30 mg/g and insulin therapy [relative excess risk due to interaction ( RERI)=2.46, 95% CI: 0.84-4.09, attributable proportion due to interaction ( AP)=0.44, 95% CI: 0.26-0.63, synergy index ( S)=2.16, 95% CI: 1.37-3.41).The UACR ≥30 mg/g and longer diabetic duration ≥10 years had both multiplicative ( OR=1.67, 95% CI: 1.00-2.76) and additive interactions ( RERI=2.02, 95% CI: 0.79-3.25, AP=0.47, 95% CI: 0.27-0.66, S=2.53, 95% CI: 1.37-4.68). Conclusions:Patients with diabetes treated with insulin, with a duration of diabetes ≥10 years and accompanied by UACR ≥30 mg/g are at higher risk of developing DR than those with a single risk factor.

Objective:To investigate the interaction of risk factors for diabetic retinopathy (DR) occurrence.Methods:A cross-sectional study was performed.A total of 6 783 diabetic patients with complete survey data from 2005 to 2018 in the National Health and Nutrition Survey database were enrolled, among which 4 426 patients were included according to inclusion criteria and were divided into non-DR diabetes group of 3 491 cases and DR group of 935 cases.The related risk factors were collected, including age, gender, race, residential status, education, annual household income, body mass index (BMI), fasting glucose, glycosylated hemoglobin, duration of diabetes, family history of diabetes, comorbidities, smoke, alcohol use, sleep, physical activity.Patient Health Questionnaire (PHQ-9) was used to assess the psychological status.After the categorization of all variables, risk factors of DR were analyzed by logistic regression, and the interaction between factors was further analyzed.Results:Multivariate analysis showed that female[odds ratio ( OR)=1.33, 95% confidence interval ( CI): 1.02-1.72], duration of diabetes ≥10 years ( OR=1.03, 95% CI: 1.02-1.04), insulin therapy ( OR=2.38, 95% CI: 1.87-3.05), urinary albumin creatinine ratio (UACR) ≥30 mg/g ( OR=1.55, 95% CI: 1.22-1.96) and depression ( OR=1.44, 95% CI: 1.13-1.83) were risk factors for DR, and BMI≤28 kg/m 2 ( OR=0.70, 95% CI: 0.55-0.89) was a protective factor for DR.Furthermore, interaction analysis revealed additive interaction between UACR ≥30 mg/g and insulin therapy [relative excess risk due to interaction ( RERI)=2.46, 95% CI: 0.84-4.09, attributable proportion due to interaction ( AP)=0.44, 95% CI: 0.26-0.63, synergy index ( S)=2.16, 95% CI: 1.37-3.41).The UACR ≥30 mg/g and longer diabetic duration ≥10 years had both multiplicative ( OR=1.67, 95% CI: 1.00-2.76) and additive interactions ( RERI=2.02, 95% CI: 0.79-3.25, AP=0.47, 95% CI: 0.27-0.66, S=2.53, 95% CI: 1.37-4.68). Conclusions:Patients with diabetes treated with insulin, with a duration of diabetes ≥10 years and accompanied by UACR ≥30 mg/g are at higher risk of developing DR than those with a single risk factor.

Objective:To investigate the incidence of visual fatigue among military pilots during flights or simulated flights and analyze the correlations among the multidimensional evaluation indicators of visual fatigue.Methods:A total of 172 pilots from an Air Force unit were selected between March 2022 and August 2023. A self-made pilot visual fatigue scale [involving the basic information, visual fatigue status scale (VFSS), and visual quality scale (VQS) was used. The visual fatigue among pilots of different types was compared. Pearson correlation analysis was used to explore the correlations between the cumulative duration of visual display terminal (VDT) and the dimensions of the VFSS, as well as between dimensions of the VFSS and the VQS. Multiple linear regression was used to identify the determinants of the score of the VQS.Results:A total of 172 questionnaires were issued, 146 of which were valid, with an effective rate of 84.88%. Among the 146 military pilots, 73 were fighter pilots and 73 were pilots of other aircraft types (20 bombers, 5 helicopters, 36 transporters, 8 trainers, and 4 fighter-bombers). There were significant differences in the scores of various dimensions and the total score of the VFSS between pilots who were different in age, aircraft types, maximum single-sortie flight durations, and in the proportion of time spent viewing cockpit displays during flight missions ( F=4.93-14.41, t=2.37-4.86, all P<0.01 or <0.05). Significant differences in visual disturbance, systemic symptoms, environmental factors, and the total visual fatigue score were observed between pilots whose total flying hours were different ( F=14.18, 4.90, 4.66, 8.12, P<0.001, =0.009,0.011, <0.001). However, there were no significant differences in the scores of any dimension or in the total score of the VFSS between pilots with a history of ocular trauma or disease and those without (all P>0.05). The cumulative duration of VDT use was positively correlated with the scores of all dimensions and the total score of the VFSS ( r=0.353, 0.303, 0.312, 0.250, 0.356, P<0.001, <0.001, <0.001, =0.002, <0.001), the dimensions of which were positively correlated with those of the VQS ( r=0.448-0.781, all P<0.01). Age ( B=1.524, 95% CI: 0.503-2.545), proportions of time spent viewing cockpit displays during flight missions ( B=3.721, 95% CI: 1.683-5.759), starburst ( B=2.346, 95% CI: 0.516-4.176), blurred vision ( B=3.517, 95% CI: 1.168-5.866), visual fluctuation ( B=2.997, 95% CI: 1.036-4.957) and halo ( B=2.415, 95% CI: 0.469-4.362) were contributors to the total visual fatigue score. Conclusions:The scores of various dimensions and the total score of visual fatigue status in military pilots can increase with age, peak in the group ages 40 to 49, and then decline. Fighter pilots experience lower levels of visual fatigue than those of other aircraft types. The visual quality scale can serve as a reference for assessing pilots′ visual fatigue status. Cumulative durations of VDT use are positively correlated with the degree of visual fatigue. Age, proportions of time spent viewing cockpit displays during flight missions, starburst, blurred vision, visual fluctuation and halo can be used to quickly assess the risk level of visual fatigue among pilots.

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 analyze the optical coherence tomography (OCT) imaging characteristics in patients with Coats disease and their value in predicting macular fibrosis.Methods:A nested case-control study was performed.A total of 43 patients (43 eyes) diagnosed with Coats disease through color fundus photography, ocular B-scan ultrasonography, fundus fluorescein angiography, and spectral-domain OCT examination were enrolled from January 2008 to October 2021 at the Xijing Hospital.Among them, there were 40 males and 3 females, aged from 2 to 60 years old, with a median age of 13 years.Macular fibrosis was used as an indicator of poor prognosis, and patients were divided into two groups based on whether macular fibrosis occurred at the end of follow-up.The differences in OCT characteristics between two groups were compared and logistic regression analysis was used to identify the risk factors for macular fibrosis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Xijing Hospital of Fourth Military Medical University (No.KY20202009-C-1).Results:The OCT clinical features of 43 cases of Coats disease included intraretinal hard exudates in 43 eyes (100%), subretinal fluid in 21 eyes (48.8%), macular cysts in 17 eyes (27.9%), subretinal exudates in 9 eyes (20.9%), anterior retinal hyperreflective dots in 7 eyes (16.3%), epiretinal membrane in 21 eyes (48.8%), and intraretinal fluid in 22 eyes (51.2%).In color fundus photos of 41 eyes, 38 eyes (93.0%) had hard exudates distributed in the posterior pole and 27 eyes (65.9%) had the mid-peripheral region.OCT examination showed that hard exudates were distributed in the inner nuclear layer in 35 eyes (81.4%) and the outer nuclear layer in 33 eyes (76.7%).Among 21 eyes with exudative retinal detachment detected by OCT, 9 eyes (42.9%) were detected by fundus photography and 18 eyes (85.7%) were detected by B-scan ultrasonography.The proportions of eyes with subretinal fluid and subretinal exudates were higher in the macular fibrosis group than in the non-macular fibrosis group, and the differences were statistically significant ( χ2=20.755, P<0.001; χ2=6.133, P=0.013).Logistic regression analysis showed that the presence of subretinal fluid was a risk factor for macular fibrosis (odds ratio=48.345, 95% confidence interval: 4.272-547.066, P=0.002). Conclusions:OCT examination can detect subretinal fluid, subretinal exudates, macular cysts, macular exudates, and hyperreflective spots in the retina of patients with Coats disease.Subretinal fluid is a risk factor for macular fibrosis.

AIM:To explore the possible mechanism of Yiqi-Huoxue formula(YQHXF)in treating cerebral ischemia-reperfusion injury.METHODS:Male SD rats were randomly divided into six groups,namely,the sham,mod-el,nimodipine,and low-,middle-and high-dose YQHXF groups.The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established in all groups except the sham group.After successful modeling,the YQHXF low-,me-dium-,and high-dose groups were given 3.8,7.5,and 15 g?kg-1?d-1 of YQHXF,respectively,by gavage,while the ni-modipine group was given 12 mg?kg-1?d-1 of nimodipine tablets by gavage.The sham and model groups were given 10 mL?kg-1?d-1 of distilled water by gavage.After 14 days of drug intervention,the rats were euthanized and the neurological func-tion was evaluated.The infarct volume was assessed using 2,3,5-triphenyltetrazolium chloride(TTC)staining and brain histopathological changes were determined by hematoxylin-eosin(HE)staining.Transmission electron microscopy was used to investigate changes in autophagosomes,with immunofluorescence used to assess expression of microtubule-associ-ated protein 1 light chain 3(LC3)protein in the cerebral cortex,Western blot was used to measure protein levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,LC3B,p62,beclin-1,and Atg5,and RT-qPCR was used to determined LC3 and P62 mRNA expression.RESULTS:Compared with the sham group,the neural function scores of rats in the model group rats were significantly increased,and TTC staining revealed large areas of white cerebral infarction.There was severe pathological damage to the cerebral tissue in the ischemic cortical area,and large numbers of autophagosomes were seen inside the cells.Immunofluorescence staining showed significant numbers of LC3B-positive cells(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly upregulated(P<0.01),while that of p62 was markedly downregulated(P<0.01).The expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was also significantly reduced(P<0.01).In addition,the mRNA expression of LC3 was significantly upregulated(P<0.01),with downregulation of P62 mRNA levels(P<0.01).Compared with the model group,both the YQHXF medium-and high-dose groups showed upregulated LC3-Ⅱ/LC3-Ⅰ values after 12 h of reperfusion(P<0.01),followed by downregulation of the ratios(P<0.05)after 3,7,and 14 days of reperfusion.Furthermore,after 14 days of reperfusion,compared with the model group,the middle-and high-dose YQHXF groups and the nimodipine group showed reduced neurological function scores(P<0.01),reduced cerebral infarction volumes(P<0.01),improvements in the pathological damage to cortical tis-sue,and reduced autophagosome formation to varying degrees.At the same time,the number of LC3B-positive cells was reduced(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly downregulated,while that of p62 was upregulated(P<0.01).The mRNA expression of LC3 and p62 was consistent with the protein levels(P<0.01).In addition,the expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was upregulated(P<0.01).CONCLUSION:YQHXF can dynamically regulate autophagy in ischemic brain tissue,with inhibition of excess autophagy by activation of the PI3K/Akt/mTOR signaling pathway,thus reducing the infarct volume,alleviating brain dam-age,and promoting the recovery of neurological function.

Cholelithiasis is a common disease of the digestive system.The risk factors for cholelithiasis have been reported and summarized many times in the published literature,which primarily focused on cross-sectional studies.Due to the inherent limitations of the study design,the reported findings still need to be validated in additional longitudinal studies.Moreover,a number of new risk factors for cholelithiasis have been identified in recent years,such as bariatric surgery,hepatitis B virus infection,hepatitis C virus infection,kidney stones,colectomy,osteoporosis,etc.These new findings have not yet been included in published reviews.Herein,we reviewed the 101 cholelithiasis-associated risk factors identified through research based on longitudinal investigations,including cohort studies,randomized controlled trials,and nested case control studies.The risk factors associated with the pathogenesis of cholelithiasis were categorized as unmodifiable and modifiable factors.The unmodifiable factors consist of age,sex,race,and family history,while the modifiable factors include 37 biological environmental factors,25 socioenvironmental factors,and 35 physiochemical environmental factors.This study provides thorough and comprehensive ideas for research concerning the pathogenesis of cholelithiasis,supplying the basis for identifying high-risk groups and formulating relevant prevention strategies.

Objective This article aims to investigate the association between hypertension and the risk of GSD by conducting a national multicenter study,a systematic review,and a meta-analysis.Methods The study was conducted in three stages.In the first stage,subjects were recruited for health examination in four hospitals in Chengdu,Tianjin,Beijing,and Chongqing,China,from 2015 to 2020,and the multivariate logistic regression analysis was used to investigate the association between hypertension and the risk of GSD in each center.In the second stage,Embase,PubMed,Wanfang Data,VIP,and CNKI databases were searched for related studies published up to May 2021,and a meta-analysis was conducted to further verify such association.In the third stage,the random effects model was used for pooled analysis of the results of the multicenter cross-sectional study and the findings of previous literature.Results A total of 633 948 participants were enrolled in the cross-sectional study,and the prevalence rate of GSD was 7.844%.The multivariate logistic regression analysis showed that hypertension was positively associated with the risk of GSD(P＜0.05).Subgroup analysis showed that there was no significant difference in the association between hypertension and GSD between individuals with different sexes,ages,and subtypes of GSD.A total of 80 articles were included in the systematic review and the meta-analysis,and the results showed that the risk of GSD was increased by 1.022 times for every 10 mmHg increase in diastolic pressure and 1.014 times for every 10 mmHg increase in systolic pressure.Conclusion Hypertension significantly increases the risk of GSD,and the findings of this study will provide a basis for the etiology of GSD and the identification of high-risk groups.