Diabetic retinopathy(DR)is one of the most common and serious microvascular complications of diabetes, posing a significant threat to patients' visual health. In recent years, epigenetic mechanisms have garnered increasing attention in the scientific community for their pivotal role in the onset and progression of DR. This paper systematically examines the regulatory roles of epigenetic mechanisms in DR, covering key pathways such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Under hyperglycemic conditions in diabetes, these epigenetic mechanisms modulate gene expression, thereby influencing critical pathological processes such as oxidative stress, inflammatory responses, mitochondrial dysfunction, and metabolic memory. This article reviews recent advances in epigenetic regulation in DR, providing an in-depth analysis of its underlying molecular mechanisms and complex regulatory networks, and explores the potential of epigenetic markers as diagnostic biomarkers and therapeutic targets. Additionally, this article highlights emerging therapeutic strategies targeting epigenetic modifications, aiming to provide a theoretical foundation and research direction for the early diagnosis and precision treatment of this disease.

OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.

Objective:To explore molecular mechanism of high-altitude hypoxia regulates PPAR signaling pathway induced ferroptosis in spleen.Methods:Hypoxia animal model was constructed,target genes were screened and predicted by combination of transcriptomics and protein omics.Key genes in PPAR and ferroptosis pathways under hypoxia exposure were explored by GO and KEGG enrichment analysis and verified by RT-qPCR and Western blot.Results:Combination of transcriptomics and protein omics showed that 95 predicted target genes(protein)showed significantly differential expression under hypoxic exposure.GO annotation analysis and KEGG enrichment analysis showed that differential genes were mainly significantly enriched in PPAR and ferroptosis signaling pathways.A negative correlation was found between PPAR and ferroptosis signaling pathways,and GSEA showed that differential gene sets of PPAR and ferroptosis signaling pathways exhibited opposite expression trend in high-altitude hypoxia group.Validation of key genes PPARA,RXRB,APOA1 and SCD-1 in PPAR signaling pathway revealed that both mRNA and protein expres-sions were down-regulated under hypoxic exposure.Subsequently,differential expression was observed in mRNA and protein expres-sions of GPX4 in endogenous pathway and SLC7A11,TRP53 and TFRC in exogenous pathway in ferroptosis signaling pathway.Corre-lations between four key genes for ferroptosis and differential inflammation-associated genes(DE-IRGs)were positively or negatively.IL-1β,IL-6,IL-12,IL-18,IFN-γ and TNF-α expressions in spleen tissue were up-regulated under hypoxic exposure.Conclusion:High-altitude hypoxia exposure further induces ferroptosis through PPAR signaling pathway-mediated lipid metabolism disorders,and accompanied by occurrence of inflammatory response,which causes damage of spleen tissue.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.

Objective:To understand the current situation and the relevant factors of the intrinsic capacity of the elderly in nursing institutions.Methods:It was a cross-sectional study. From December 2023 to February 2024, a total of 10 elderly people living in 5 institutions in Huaihua City, Hunan Province, 3 institutions in Changsha City, and 2 institutions in Yinchuan City, Ningxia Hui Autonomous Region, were conveniently selected. Relevant clinical data of the participants were collected through questionnaires. The 5 dimensions of motor, psychological, cognitive, vitality, and perceptual were selected to evaluate the intrinsic capacity of the participants, and their total intrinsic capacity scores were calculated by using the Short Physical Performance Battery, Geriatric Depression Scale, Mini-mental State Examination, Short-Form Mini-Nutritionalas Assessment and the Complaints Sensory Functioning, respectively. Multiple linear stepwise regression models were used to analyze the correlates of intrinsic competence in older adults in nursing facilities.Results:Two hundred and seventy institutionalized older adults were included in the analysis, aged (80.9±8.5) years, 117(43.33%) were male, and the length of residence in an institution was 1.50(0.83, 3.00) years.The intrinsic capacity score of the 270 institutionalized older adults was 2.24±0.97, of which 265(98.15%) had declining intrinsic capacity and 5(1.85%) had good intrinsic capacity. The results of multiple linear stepwise regression analysis showed that literacy level, economic source, occupation, frequency of exercise, use of smartphones, use of elderly mobility aids, and whether or not the elderly living in the nursing home received financial support from the state were independently associated with the intrinsic ability of the elderly living in the nursing home (all P<0.05). Conclusions:The overall level of intrinsic capacity of the investigated elderly in nursing homes is low, and literacy level, economic source, occupation, use of smartphones, use of elderly mobility aids, and whether the nursing home receives state financial support are independent correlates of the intrinsic ability of the elderly in nursing homes.

Objective:To investigate the impact of para-tumoral micro-metastasis(PTMM) and other clinicopathological characteristics on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:This is a retrospective cohort study. Clinical data from 137 ICC patients who underwent radical resection at the Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital, Fudan University, between January 2017 and December 2022 were analyzed retrospectively. The cohort included 91 males and 46 females, with age ( M(IQR)) of 63 (13) years (range: 32 to 82 years). Kaplan-Meier curves were used to estimate median survival times, while Log-rank tests assessed differences in overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate Cox regression models were employed to identify factors associated with OS and RFS. Results:The median OS for all 137 ICC patients was 34 months, with 1-, 2-, and 3-year OS rates of 90.7%, 69.4%, and 39.5%, respectively. The results of univariate and multivariate Cox analysis showed that Child-Pugh grade, CA19-9, carcinoembryonic antigen, and PTMM were independent prognostic factors for OS in ICC patients after radical resection (all P<0.05), Child-Pugh grade, maximum tumor diameter, whether lymph node metastasis, and PTMM were independent prognostic factors for RFS in radical resection in ICC patients (all P<0.05). PTMM-positive patients had a median OS of 21 months and median RFS of 12 months, whereas PTMM-negative patients exhibited a median OS exceeding 60 months and median RFS of 36 months. Log-rank tests demonstrated statistically significant differences in OS and RFS between PTMM-positive and PTMM-negative patients ( P<0.01 and P=0.001, respectively). Conclusion:Preliminary findings suggest that PTMM holds significant prognostic value in evaluating outcomes for ICC patients undergoing curative resection.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS).Methods:This retrospective cohort study enrolled patients aged ≥45 years who were diagnosed with ACAOS by coronary computed tomography angiography (CTA) at the Affiliated Hospital of Xuzhou Medical University between January 1, 2011, and December 31, 2018. Baseline clinical data and coronary CTA images were collected. Anatomic imaging features were extracted, including ACAOS subtype, course of the anomalous vessel, and ostial angle. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac death, and coronary revascularization. The Maxstat method was used to determine the cut-off values of specific anatomical features for predicting MACE risk. Cox proportional hazards models were employed to analyze the impact of these imaging features on MACE in middle-aged and elderly ACAOS patients.Results:A total of 203 patients were enrolled, aged (60.0(51.0, 66.0)) years, including 119 (58.6%) males. Over a follow-up of (98.2±30.9) months, 39 patients experienced MACE. Maxstat identified an optimal cut-off value of 34.3° for the ostial angle of the anomalous vessel. Multivariable Cox proportional hazards regression analysis revealed that the following factors were independent risk factors for MACE: left-sided ACAOS subtype ( HR=4.35, 95% CI 2.17-8.73, P<0.001), an interarterial course between the aorta and pulmonary artery ( HR=3.21, 95% CI 1.23-8.37, P=0.017), an anomalous vessel ostial angle <34.3° ( HR=2.62, 95% CI 1.18-5.77, P=0.017), and concomitant coronary artery disease ( HR=2.92, 95% CI 1.49-5.73, P=0.002). Conclusion:In middle-aged and elderly patients with ACAOS, the imaging anatomical features of a left-sided ACAOS subtype, an interarterial course, and an ostial angle <34.3° are independent risk factors for MACE.