Research indicates that microbe activity within the human body significantly influences health by being closely linked to various diseases.Accurately predicting microbe-disease interactions(MDIs)offers critical insights for disease intervention and pharmaceutical research.Current advanced AI-based technologies automatically generate robust representations of microbes and diseases,enabling effec-tive MDI predictions.However,these models continue to face significant challenges.A major issue is their reliance on complex feature extractors and classifiers,which substantially diminishes the models' generalizability.To address this,we introduce a novel graph autoencoder framework that utilizes decoupled representation learning and multi-scale information fusion strategies to efficiently infer po-tential MDIs.Initially,we randomly mask portions of the input microbe-disease graph based on Bernoulli distribution to boost self-supervised training and minimize noise-related performance degradation.Secondly,we employ decoupled representation learning technology,compelling the graph neural network(GNN)to independently learn the weights for each feature subspace,thus enhancing its expressive power.Finally,we implement multi-scale information fusion technology to amalgamate the multi-layer outputs of GNN,reducing information loss due to occlusion.Extensive experiments on public datasets demonstrate that our model significantly surpasses existing top MDI prediction models.This indicates that our model can accurately predict unknown MDIs and is likely to aid in disease discovery and precision pharmaceutical research.Code and data are accessible at:https://github.com/shmildsj/MDI-IFDRL.

Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective:To investigate the clinical features, pathologic characteristics, treatment and prognosis of primary mediastinal large B-cell lymphoma (PMBCL) in children.Methods:Clinical data including clinical manifestations, treatment, clinical efficacy of 8 cases of childhood PMBCL treated in Beijing Children′s Hospital, Capital Medical University from March 2017 to February 2024 were collected retrospectively, the clinical characteristics and prognosis of them were summarized.Results:Among the 8 children, there were 5 males and 3 females. The age at the time of initial diagnosis was 11.0 (10.3, 13.5) years. The first clinical symptoms were cough (8 cases) and stridor (6 cases). The lesions most often involved the mediastinum (8 cases), lungs (5 cases, hilum more often), pericardium (5 cases), and pleura (4 cases). Extra thoracic invasion was present in 4 cases, 7 cases had huge tumor lesions and 7 cases were phase Ⅲ clinical stage. Except for 1 case who underwent surgical resection of the tumor, the remaining 7 cases were treated with DA-EPOCH+R (dose adjusted-etoposide+prednisone+vincristine+cyclo-phosphamide+doxorubicin+rituximab) chemotherapy. The follow-up time was 25.0 (10.5, 43.3) months, with 7 cases in complete and partial metabolism response, 1 case had disease progression. All 8 cases survived.Conclusions:PMBCL is most common in school-age boys and most of them present with huge mediastinal tumor focus. PMBCL expresses B-cell spectrum antigens and weakly expresses CD30.The application of DA-EPOCH+R is effective in the treatment of PMBCL in children.

Stress refers to the non-specific responses of a stimulated body to different stressors and the subsequent maintenance or restoration of internal environmental homeostasis.Adverse stress reactions lead to general balance disruption and may cause digestive,neurological,and endocrine disorders,and decreased immune capacity,which seriously impact host health.As the core compo-nent of intestinal micro-ecology,the intestinal flora can greatly alter its own composition,distribu-tion,function,metabolic product output,and other aspects during stress,which cause disorders and aggravate homeostatic imbalance in internal environments.While the intestinal flora is of great sig-nificance to animal medicine and agricultural production,little is known about stress and its impact on intestinal flora.Therefore,we briefly reviewed the impact of stress on animal intestinal flora in combination with the latest research and provided theoretical insights on intestinal health research.

Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P＜0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P＜0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P＜0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P＜0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P＜0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P＜0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P＜0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

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

Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

Research indicates that microbe activity within the human body significantly influences health by being closely linked to various diseases. Accurately predicting microbe-disease interactions (MDIs) offers critical insights for disease intervention and pharmaceutical research. Current advanced AI-based technologies automatically generate robust representations of microbes and diseases, enabling effective MDI predictions. However, these models continue to face significant challenges. A major issue is their reliance on complex feature extractors and classifiers, which substantially diminishes the models' generalizability. To address this, we introduce a novel graph autoencoder framework that utilizes decoupled representation learning and multi-scale information fusion strategies to efficiently infer potential MDIs. Initially, we randomly mask portions of the input microbe-disease graph based on Bernoulli distribution to boost self-supervised training and minimize noise-related performance degradation. Secondly, we employ decoupled representation learning technology, compelling the graph neural network (GNN) to independently learn the weights for each feature subspace, thus enhancing its expressive power. Finally, we implement multi-scale information fusion technology to amalgamate the multi-layer outputs of GNN, reducing information loss due to occlusion. Extensive experiments on public datasets demonstrate that our model significantly surpasses existing top MDI prediction models. This indicates that our model can accurately predict unknown MDIs and is likely to aid in disease discovery and precision pharmaceutical research. Code and data are accessible at: https://github.com/shmildsj/MDI-IFDRL.