Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

The major histocompatibility complex plays a crucial role in the immune response process, which is closely related to the occurrence and development of tumors and organ transplantation. Cellular immunity occupies an important position in tumor immunity and organ transplantation immunity, while humoral immunity also plays a significant role in organ transplantation immunity. Organ transplantation requires the induction and maintenance of immune tolerance, while tumors develop immune escape phenomena during their progression. In-depth exploration and comparison of the mechanisms of tumor immune escape and organ transplantation immune tolerance are of great significance for formulating reasonable immune tolerance induction strategies, improving the quality of life and prolonging the survival time of organ transplant patients.

ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) among underground coal mine workers, identify the risk factors for WMSDs, and provide a scientific evidence for the prevention and treatment of WMSDs.Methods:In March 2024, through cluster sampling, the on-the-job workers who underwent questionnaire surveys and health examinations at a certain coal mine from July to August 2018 were selected as the research subjects. Basic information of employees, ergonomics-related characteristics, and the occurrence status of WMSDs in each part were collected, and multivariate logistic regression was used for analysis.Results:The incidence rate of WMSDs in at least one site among underground coal mine workers within the past year was 62.22% (219/352). The top three sites in sequence were the lower back (44.32%, 156/352), neck (26.14%, 92/352), and knee (26.14%, 92/352). Multivariate logistic regression analysis showed that frequently exerting great force with arms or hands during work ( OR=2.223, 95% CI: 1.022-4.836), prolonged static forward bending ( OR=1.544, 95% CI: 1.305-1.972), and frequently exerting great effort to operate tools or machines ( OR=2.206, 95% CI: 1.011-4.813), absence of external support systems ( OR=1.589, 95% CI: 1.349-1.996), and repetitive full-body twisting ( OR=1.523, 95% CI: 1.298-1.916) were all risk factors for the occurrence of WMSDs in the lower back ( P<0.05). Both night shift work ( OR=1.564, 95% CI: 1.339-1.939) and frequent forward neck flexion ( OR=1.532, 95% CI: 1.312-1.907) were all risk factors for the occurrence of WMSDs in the neck ( P<0.05). Lifting heavy objects above the shoulder ( OR=1.333, 95% CI: 1.142-1.782), uncomfortable posture and inability to exert force ( OR=1.873, 95% CI: 1.104-2.712), the use of vibration tools ( OR=2.958, 95% CI: 1.255-6.972), and length of service >10 years ( OR=1.525, 95% CI: 1.105-1.967) were all risk factors for the occurrence of WMSDs in the knee ( P<0.05) . Conclusion:The incidence of WMSDs among underground coal miners is relatively high, mainly concentrated in the lower back, neck and knee, and is related to factors such as poor working postures, and work organization. Coal mining enterprises should strengthen work organization, provide appropriate working equipment, and ensure reasonable distribution of workloads.

Objective:To identify risk factors influencing the incidence of hypertension among steelworkers (Homo sapiens) and establish an effective and easily implementable hypertension prediction model.Methods:In September 2023, 2214 steelworkers (Homo sapiens) were selected as study subjects. Basic demographic information, lifestyle, and occupational exposure data were collected, along with physiological measurements such as height, weight, and blood pressure. Multivariate unconditional logistic regression analysis was employed based on relevant literature to determine influencing factors for hypertension among steelworkers (Homo sapiens). Python 3.9 software was used to construct and compare logistic regression, support vector machine (SVM), random forest, extreme gradient boosting tree (XGBoost), and LGBM models. Model performance was evaluated using metrics such as receiver operating characteristic (ROC) curves, accuracy, calibration curves, and F1 scores. The Shapley Additive Explanations (SHAP) model was introduced for feature importance analysis to enhance the interpretability of the prediction model.Results:A total of 432 cases of hypertension were detected among 2214 study subjects, with a detection rate of 19.51%. Age, smoking status, salt intake, use of cooling equipment, carbon monoxide exposure, family history of hypertension, fasting blood glucose, triglycerides, and hemoglobin were identified as independent risk factors for hypertension ( P<0.05). A comparison of the five models revealed the following performance metrics: logistic regression achieved an accuracy of 0.853, F1 score of 0.680, Brier score of 0.108, and AUC of 0.907; SVM demonstrated an accuracy of 0.863, F1 score of 0.687, Brier score of 0.081, and AUC of 0.910; random forest showed an accuracy of 0.857, F1 score of 0.603, Brier score of 0.105, and AUC of 0.861; XGBoost yielded an accuracy of 0.850, F1 score of 0.684, Brier score of 0.117, and AUC of 0.899; and the LGBM model exhibited an accuracy of 0.838, F1 score of 0.625, Brier score of 0.112, and AUC of 0.870. Conclusion:The SVM model demonstrated strong predictive performance, effectively assessing the risk of hypertension among steelworkers (Homo sapiens) and facilitating targeted health management interventions.

Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

Objective:To analyze the factors influencing the lung function of coal miners, identify the optimal combination of indicators for evaluating lung function, develop a risk assessment model using machine learning, and offer personalized risk assessment for workers.Methods:In June 2023, through cluster sampling, male underground workers who participated in occupational health examinations at a coal mine in North China from July to August 2018 were selected as the research subjects. Their health examination results and occupational environmental data were collected. A total of 3, 320 coal miners were included. Randomly divide the research subjects into a training set (2324 people) and a validation set (996 people) in a ratio of 7∶3, and the balance of the two sets was tested. Perform LASSO regression analysis using R 4.2.2 software to select relevant important variables, and determine the model's input variables by combining them with relevant literature. Utilize Python 3.8 to construct logistic regression, random forest, support vector machine, and XG Boost models, assess the models' discriminative ability using metrics like accuracy, sensitivity, specificity, F1 score, ROC curve, and AUC, evaluate the models' calibration using Brier score, Log loss score, and calibration curve, and further analyze the clinical performance of the developed models through DCA decision curve analysis.Results:Among the 3 320 coal miners, 856 had abnormal lung function (25.78%). The XG Boost model was identified as the optimal model, achieving a training set accuracy of 87.39%, sensitivity of 86.60%, specificity of 87.67%, F1 score of 0.779, AUC of 0.945, Brier score of 0.071, Log loss of 0.267 and demonstrated good calibration curve consistency.Conclusion:The XG Boost model exhibits superior predictive performance compared to other models, and the model has high application value. The Shapley Additive Explanation (SHAP) method is employed for interpretation, making it a reliable basis for preventing abnormal lung function in coal miners.