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 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 clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy.Methods:Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People′s Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed.Results:All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months).Conclusions:The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

Objective:To investigate the clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy.Methods:Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People′s Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed.Results:All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months).Conclusions:The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

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 compare the efficacy of three different methods in the prevention of adhesion after the HEOS system for different degrees of intrauterine adhesions.Methods 284 patients with mild,moderate and severe intrauterine adhesions,who were treated with the HEOS system,were divided into three groups,the intrauterine device with sodium hyaluronate gel was placed in Group A,Foley water capsule tube with sodium hyaluronate gel was placed in Group B,and sodium hyaluronate gel was placed in Group C only.The recovery of uterine adhesion,improvement of menstruation,endometrial thickness,and adverse reactions were compared among the three groups.Results The mild intrauterine adhesions group showed statistical differences among the three groups(P<0.05).Group A had a higher menstrual improvement rate than Group C(P<0.017),and there was no significant difference in other therapeutic indicators(P>0.017).However,the adverse reaction rate in Group A was also higher than that in Group C(P<0.017).In the moderate intrauterine group,there was a significant difference in the improvement rate of intrauterine adhesions between Group B and the other two groups(P<0.017).Group A and B were higher than Group C in terms of menstrual status,endometrial thickness,and adverse reactions(P<0.017).In severe intrauterine adhesions,Group A had higher efficacy indicators than other groups(P<0.017).Conclusions The curative effect index and adverse reaction rate were analyzed,after operation.For the light,moderate,and severe intrauterine adhesions,sodium hyaluronate gel,Foley water capsule tube with sodium hyaluronate gel,and intrauterine device with sodium hyaluronate gel were the best choice for adhesion.Individual and hierarchical management can achieve good clinical effects,which is worth popularizing.

OBJECTIVE To study the preparation technology based on quality by design (QbD) concept of Erdong decoction particles, and to control its quality. METHODS Design L9(34) orthogonal test method, and the extraction process of Erdong decoction was optimized by AHP-CRITIC mixed weighted method with the extract rate, index component transfer rate and total polysaccharide as evaluation indexes. Taking ratio of briquetting, dissolution rate, angle of repose and moisture absorption rate as indexes, the central composite design-response surface methodology method combined with entropy weight method was used to optimize the forming process of Erdong decoction granules. The relative homogeneity index, bulk density, vibration density, moisture, hygroscopicity, angle of reposition and Hausner ratio were used as indicators to establish a physical fingerprint to evaluate particle quality consistency. RESULTS The optimal extraction process of Erdong decoction was to add 12 times of water without soaking and extract it 3 times for 30 min each time. The mean comprehensive score of the three batches of repeated validation tests was 54.24, and the RSD was 1.09%. The optimum molding process of Erdong decoction granules was as follows: the ratio of dry paste powder to auxiliary material was 1∶0.6, the volume fraction of wetting agent was 87%, the amount of wetting agent was 16%, and it was dried at 80 ℃ for 30 min. The similarity of physical fingerprints of 5 batches of particles was>0.99. CONCLUSION The method is stable and feasible, which can provide direction for the industrial production of Erdong decoction granules and the further research of this preparation.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. 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 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.