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 verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

In the period of digital transformation of the medical service model， maintaining algorithm justice for medical artificial intelligence possesses multiple value implications. However， practical dilemmas exist at different stages of achieving this value goal. At the initial stage of diagnosis and treatment decision-making， there is a risk of imbalance in patients’ rights and interests， such as weakened effectiveness of patients’ right to informed consent， as well as low synergy between rights and interests protection and technological innovation. In the process of diagnosis and treatment decision-making， the algorithmic model is constrained by the technological bottleneck in the underlying application， deviating from the legal track of technological neutrality. After the diagnosis and treatment decision-making is generated， it triggers a crisis in the remedy of patients’ rights and interests and breeds the phenomenon of an ambiguous definition of subject qualification and attribution principle. In this regard， it is essential to establish a preemptive safeguard system focusing on the protection of patients’ rights and interests， set technological fairness standards， and shape review norms of technological neutrality. The aim is to ensure the equalization of remedy channels for patients’ rights and interests， promote the fairness in the proportion of responsibilities among multiple subjects， and thereby safeguard the digital justice in the field of intelligent diagnosis and treatments.

ObjectiveTo observe the clinical efficacy and safety of lung-boosting moxibustion with different moxibustion doses in the treatment of stable chronic obstructive pulmonary disease （COPD）. MethodsA total of 240 stable COPD patients with lung qi deficiency， lung-spleen qi deficiency， or lung-kidney qi deficiency syndrome were enrolled， all receiving standardized western medical treatment and lung-boosting moxibustion. According to the thickness of the moxa wool， the thickness of the ginger paste， and the treatment duration， patients were randomly divided into eight groups， which were Group A （3.0 cm thickness moxa， 2.5 cm ginger mud， 60 min treatment time）， Group B （3.0 cm thickness moxa， 2.5 cm ginger mud， 90 min treatment time）， Group C （2.0 cm thickness moxa， 2.5 cm ginger mud， 60 min treatment time）， Group D （2.0 cm thickness moxa， 2.5 cm ginger mud， 90 min treatment time）， Group E （3.0 cm thickness moxa， 2.0 cm ginger mud， 60 min treatment time）， Group F （3.0 cm thickness moxa， 2.0 cm ginger mud， 90 min treatment time）， Group G （2.0 cm thickness moxa， 2.0 cm ginger mud， 60 min treatment time）， Group H （2.0cm thickness moxa， 2.0cm ginger mud， 90 min treatment time）. Treatment was performed once every 15 days for 3 months， with a total of six sessions. The primary outcomes were the scores of the clinical symptoms and signs questionnaire for stable COPD before and after treatment， comprising seven symptom domains （cough， sputum production， wheezing， chest tightness， shortness of breath， fatigue， and cyanosis） and the total score. The secondary outcomes included the scores of the modified COPD patient-reported outcome questionnaire （mCOPD-PRO） involving the physical， psychological， and environmental domains and the total score， the scores of the modified Effectiveness Satisfaction Questionnaire for COPD （mESQ-COPD） involving clinical symptoms， work and daily living capacity， environmental adaptability， treatment efficacy， and the total score before and after treatment， the moxibustion sensation scores （heat sensation score and special sensation intensity score） during treatment， and cutaneous temperature （the maximum temperature achieved， the duration of temperature maintained at ≥43 ℃， and the time required to reach 43 ℃）. The safety evaluation was carried out after treatment. ResultsDuring the study， 18 patients withdrew， and 222 patients were included in the per-protocol set for analysis， including 27 in Group A， 28 in Group B， 28 in Group C， 29 in Group D， 27 in Group E， 28 in Group F， 27 in Group G， and 28 in Group H. After treatment， the total score on the clinical symptoms and signs questionnaire， as well as the cough and chest tightness symptom scores in Group F were significantly lower than those in other groups （P＜0.05）. Group F demonstrated statistically lower total mCOPD-PRO score and physical domain score （P＜0.05）， lower total mESQ-COPD score and the scores for clinical symptoms and treatment efficacy （P < 0.05）， as well as higher heat sensation score （P＜0.05） than other groups. The maximum temperature was significantly higher in Group E and Group F than in the other groups， while the duration of temperature maintained at ≥43 ℃ was significantly longer in Group F than other groups， and the time required to reach 43 ℃ was significantly shorter in Group E and Group F than in Groups C， D， G， and H （P＜0.05）. No significant abnormalities were observed in routine blood tests， liver function， renal function， urinalysis， or electrocardiograms before and after treatment in any group. No serious adverse events occurred during the treatment period. ConclusionThere are differences in the efficacy of different moxibustion doses of lung-boosting moxibustion in the treatment of stable COPD. Moxibustion with 3.0 cm thickness moxa， 2.0 cm ginger mud， and 90 min treatment time can obtain relatively superior efficacy while demonstrating a favorable safety profile.

Objective: To examine the association between academic stress and anxiety-depression comorbidity among college students and the potential moderating effect of physical activity, so as to provide a theoretical basis for the development of evidence based mental health promotion frameworks in higher education institutions. Methods: From October 2022 to June 2024, a total of 7 980 students from 21 universities across five provinces/municipalities in China, including Shanghai, Jiangsu, Zhejiang, Shandong, and Anhui, using a combination of convenience sampling and stratified random cluster sampling. Physical activity, academic stress, anxiety, and depression were assessed by using the 24 hour Movement Behaviors Questionnaire, the Chinese College Students Mental Health Screening Scale, the Generalized Anxiety Disorder-7, and the Center for Epidemiologic Studies Depression Scale, respectively. Binary Logistic regression was used to examine the associations between academic stress and anxiety, depression, and their comorbidity. The PROCESS macro was employed to test the moderating effect of physical activity. Results: The prevalence of anxiety-depression comorbidity among college students was relatively high (11.53%), with significant differences observed across grades and body mass index (BMI) categories ( χ 2=70.30, 24.63, both P <0.01). Binary Logistic regression revealed that, compared with low academic stress, moderate academic stress among male students was significantly associated with greater odds of anxiety ( OR =2.78), depression ( OR =2.75), and anxiety-depression comorbidity ( OR =2.89) (all P <0.01). High academic stress was associated with elevated odds of anxiety ( OR =6.66), depression ( OR =12.81), and anxiety-depression comorbidity ( OR =13.65) (all P <0.01). Among female students, moderate academic stress was associated with anxiety ( OR =2.58), depression ( OR =1.52), and anxiety-depression comorbidity ( OR =1.70) (all P <0.01). High academic stress increased the risk of anxiety ( OR =6.77), depression ( OR =6.81), and anxiety-depression comorbidity ( OR =7.48) (all P <0.05). The moderation analysis indicated that the interaction between total physical activity duration and academic stress had a significant netative moderating effect on anxiety-depression comorbidity among college students ( β =-0.03, P <0.01). Conclusions Academic stress increases the risk of anxiety, depression, and anxiety-depression comorbidity among college students. Physical activity may attenuate the adverse effects of academic stress on anxiety-depression comorbidity.

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

This paper focuses on the application of health big data in cancer screening. Firstly, the sources and characteristics of health big data are introduced, then the commonly used epidemiological designs and analytical techniques in hospital-based cancer screening studies are summarized and the application scenarios of such studies are described. Finally, the challenges and future development in the application of health big data are analyzed to provide reference for the future studies.

Objective:To explore the trend of influenza positive rate in Beijing by using classic autoregressive integrated moving average (ARIMA) model, autoregressive integrated moving average model with exogenous variables (ARIMAX) and vector autoregression model (VAR) to compare the performance of three models in influenza prediction and select the most suitable one for Beijing.Methods:The weekly positive rate of influenza virus nucleic acid test and meteorological data in Beijing from week 1 of 2013 to week 40 of 2024 were collected. The data were divided into four groups with expanding training sets and corresponding testing sets. The training set of the first group was from week 1 of 2013 to week 40 of 2016, and the testing set was from week 41 of 2016 to week 40 of 2017. Subsequent groups extended the training set by one year each time. Data from 2020 to 2023 were excluded due to COVID-19 pandemic. The fourth group used data from the week 1 of 2013 to week 40 of 2023 for training and from the week 41 of 2023 to week 40 of 2024 for testing.Results:The incidence of influenza had seasonality in Beijing with higher incidence in winter and spring. The positive rate of influenza virus was positively correlated with the weekly average atmospheric pressure ( r=0.482, P<0.001) and weekly average wind speed ( r=0.003, P=0.034), and negatively correlated with the weekly average temperature ( r=-0.541, P<0.001). The ARIMAX model incorporating meteorological factors had the best prediction performance, with test set's root mean square error ( RMSE) of 0.115 3 and mean absolute error ( MAE) of 0.076 7 (the RMSE and MAE values for ARIMA and VAR models were 0.117 1 and 0.163 8, and 0.078 6 and 0.122 3, respectively). The prediction results of the optimal model showed that the positive rate of influenza virus would continue to rise in Beijing after October 2024 and reach peak in the second week of 2025, but the peak positive rate would be lower than that of previous influenza season. Conclusions:Compared with the ARIMA model and the VAR model,the ARIMAX model which used meteorological parameters is more suitable for prediction of long-term influenza trend in Beijing. The influenza trend peak was predicted to occur in the second week of 2025, but lower than that in previous influenza season.

Objective:To identify the risk factors associated with conversion to cesarean delivery in parturients receiving epidural labor analgesia and to construct a predictive model.Methods:In this prospective cohort study, 718 parturients with a singleton fetus at 37-42 weeks of gestation age, aged 22-45 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ, who received epidural labor analgesia at the Women′s Hospital affiliated to Zhejiang University School of Medicine between November 2022 and August 2023, were included and divided into 2 groups based on the final mode of delivery: cesarean delivery group (CD group) and vaginal delivery group (VD group). Data collected included maternal age, height, body mass index at labor onset, gestational age, pregnancy complications, mode of conception, parity, premature rupture of membranes, mode of labor onset and details of labor analgesia. Risk factors for conversion to cesarean delivery were analyzed using multivariate logistic regression analysis, and a prediction model was developed. The receiver operating characteristic curve was ploted, and the area under the receiver operating characteristic curve was calculated to evaluate the accuracy of the predictive model.Results:A total of 682 parturients were included in the final statistical analysis, with 103 in CD group and 579 in VD group. Multivariate logistic regression analysis showed that maternal age≥35 yr, height<160 cm, body mass index at labor onset ≥28 kg/m 2, nulliparous parturients, the use of Foley balloon catheter or dinoprostone suppositories for cervical ripening were risk factors for cesarean delivery, and cervical dilation during analgesia was a protective factor. The area under the receiver operating characteristic curve for the predictive model constructed based on the aforementioned influencing factors yielded predicting conversion to cesarean delivery due to failed vaginal trial of labor was 0.791 (95% confidence interval 0.744-0.837, P<0.001), with a sensitivity of 73.6% and a specificity of 70.9%. Conclusions:Nulliparous parturients, maternal age≥35 yr, height<160 cm, body mass index at labor onset≥28 kg/m 2, and the use of Foley balloon catheter or dinoprostone suppositories for cervical ripening are risk factors for cesarean delivery, and cervical dilation during analgesia is a protective factor. The predictive model established based on these influencing factors has high predictive performance.