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.

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.

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.

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells

Background: Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy. Raw pieces of Rhei Radix et Rhizoma (RP) are known for their strong laxative effects, often accompanied by side effects, while steamed Rhei Radix et Rhizoma pieces (SP) possess a milder laxative effect and are widely used clinically. However, there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness, particularly from a bioavailability perspective. Objective: This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics, tissue distribution, and excretion assays. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites. Pharmacokinetic, tissue distribution, and excretion assays were conducted in constipation rats following oral administration of RP and SP. Blood, tissue, urine, and fecal samples were collected and analyzed to compare the absorption, distribution, metabolism, and excretion profiles of anthraquinones, highlighting differences in bioavailability and safety between RP and SP. Results: Compared with the RP group, the SP group showed significantly reduced area under the plasma concentration-time curve, mean residence time, and half-life time values for rhein-8-O-β-D-glucopyranoside, rhein, emodin, aloe-emodin, and their glucuronide metabolites. The clearance values were significantly increased in the SP group. These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP. Additionally, these components were primarily distributed in the large intestine, where they exerted their laxative effects. Glucuronide metabolites were mainly excreted through urination, while prototype components were excreted in both urine and feces. Notably, the cumulative excretion of aloe-emodin, emodin, rhein, and their glucuronide metabolites was significantly higher in both urine and feces after SP administration, indicating that SP enhances the excretion of these components compared with RP. Conclusion: The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion, demonstrating that the steaming process significantly promotes the elimination of key components. This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma, offering a scientific basis for the improved safety and clinical use of SP. These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines. This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

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.