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.

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 Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

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: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.

Thyroid nodules are a common endocrine disorder with complex pathogenesis that remains incompletely understood. In recent years, studies have revealed that the gut microbiota may play a critical role in the occurrence and progression of thyroid nodules. This review systematically summarizes the current research progress on the association between gut microbiota and thyroid nodules, with a particular focus on potential mechanisms through which gut dysbiosis influences nodule formation via immune regulation, metabolic pathways, and gut barrier function. Evidence suggests that reduced gut microbial diversity, decreased abundance of specific beneficial bacteria, and an increased proportion of pro-inflammatory bacteria may contribute to a pro-inflammatory environment and metabolic disturbances associated with thyroid nodules. Furthermore, this review explores the potential of interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation in modulating gut microbiota and improving thyroid nodule outcomes. Although direct clinical evidence is currently lacking, the regulation of gut microbiota has emerged as a promising direction for the diagnosis and treatment of thyroid nodules, demonstrating significant clinical potential. Future efforts should focus on advancing basic and clinical research strategies to facilitate the translational application of findings in this field.

BACKGROUND:Metformin is currently considered the first-line medication for the treatment of type 2 diabetes.Metformin may delay the progression of osteoarthritis,but its specific mechanism of action remains unclear.OBJECTIVE:To evaluate the therapeutic effects and the related action mechanisms of metformin on osteoarthritis in rats.METHODS:(1)Network pharmacology:Potential common targets for metformin,osteoarthritis,and ferroptosis were screened using the CTD,SwissTargetPrediction,GeneCards,and OMIM databases.After importing the targets into the STRING database,protein-protein interaction analysis was conducted to identify the key targets for metformin,osteoarthritis,and ferroptosis.(2)Molecular docking:P53 and its downstream factor SLC7A11 protein structures in PDB format were downloaded from the PDB database.The 2D structure of metformin was converted to a 3D structure,and molecular docking of metformin with the proteins was performed using Discovery Studio 2019 Client.(3)In vivo experiments:Thirty male SD rats were randomly divided into three groups(n=10).The blank group did not receive surgery.The osteoarthritis model was established using the modified Hulth method for the model and metformin groups.One day after the surgery,rats in the metformin group were gavaged with metformin 200 mg/kg per day,while the blank and model groups were gavaged with physiological saline.Treatment continued for 4 weeks.Hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the pathological morphology and structure of the knee cartilage,and Mankin scoring was performed.ELISA was used to measure the levels of tumor necrosis factor-α and interleukin-6 in the serum.The microplate method was used to measure serum ferroptosis-related indicators,including glutathione,malondialdehyde,and Fe2+.Immunofluorescence staining,western blot assay,and real-time qPCR were used to detect the protein and mRNA expression of P53,SLC7A11,glutathione peroxidase 4,proteoglycans,and matrix metalloproteinase 13 in the cartilage tissue of the rats.RESULTS AND CONCLUSION:(1)A total of 96 intersecting targets among metformin,osteoarthritis,and ferroptosis were identified.After protein-protein interaction analysis,77 potential targets were found.Further screening identified the core targets as TP53,AKT1,JUN,interleukin-6,MYC,interleukin-1β,and tumor necrosis factor-α,among others.(2)Docking analysis results showed that metformin bound strongly and stably with P53 and its downstream factor SLC7A11.(3)In the model group,the knee cartilage surface was irregular,with cartilage tissue defects and reduced chondrocyte numbers.Compared to the model group,the knee cartilage structure damage in the metformin group was significantly improved,with a smoother cartilage surface and increased chondrocyte numbers.The Mankin score in the model group was significantly higher than that in the blank group,while the Mankin score in the intervention group was significantly lower than that in the model group.(4)Compared with the model group,the metformin group had significantly lower levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and Fe2+,and significantly higher glutathione levels.(5)Compared to the model group,the metformin group had significantly increased protein and mRNA expression of SLC7A11,glutathione peroxidase 4,and proteoglycans,and significantly decreased protein and mRNA expression of P53 and matrix metalloproteinase 13 in their cartilage tissue.(6)The results indicate that metformin can effectively improve cartilage damage in osteoarthritis rats and alleviate chondrocyte ferroptosis by inhibiting the aberrantly activated P53/SLC7A11/glutathione peroxidase 4 signaling pathway.This improvement in chondrocyte iron metabolism and lipid peroxidation response further reduces cartilage matrix degradation and prevents further cartilage damage and inflammatory response.