BACKGROUND:How to improve the hematopoietic microenvironment is a hot topic in the treatment of aplastic anemia. OBJECTIVE:To explore the action mechanism of Angelica sinensis polysaccharide in the treatment of aplastic anemia by combining GEO sequencing analysis,network pharmacology,and experimental validation. METHODS:Aplastic anemia-related differentially expressed genes were obtained from GEO database,and gene ontology and gene set enrichment analysis were performed.The active components and targets of Angelica sinensis polysaccharide were obtained by combining the literature with PubChem,SwissTargetPrediction,and PharmMapper databases.After the intersection targets were taken,STRING and Cytoscape were used to construct protein-protein interaction network,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed.Mouse model of aplastic anemia was established,and the effect and action mechanism of Angelica sinensis polysaccharide on aplastic anemia were verified by blood cell analyzer,flow cytometry,ELISA,immunohistochemistry,immunofluorescence,and western blot assay. RESULTS AND CONCLUSION:(1)A total of 834 differentially expressed genes were screened,which were involved in biological processes such as cell development,hematopoiesis,and myeloid cell differentiation.(2)347 targets related to Angelica sinensis polysaccharide were retrieved and 77 potential therapeutic genes were screened.Among them,the degree values of angiogenic,apoptotic,and immune-related factors such as VEGFA,EGLN1,Bcl-2,interferon-γ,interleukin-2,interleukin-4,and interleukin-6 were significant.(3)KEGG pathway enrichment analysis revealed that the therapeutic targets were mainly enriched in Th17 cell differentiation,NK-related cytotoxicity,cell adhesion factors such as interferon-γ,interleukin-2,and interleukin-4 related signaling pathways.(4)Animal experiments showed that Angelica sinensis polysaccharide significantly improved bone marrow haematopoiesis,increased peripheral blood cell,and bone marrow single nucleated cell counts,and improved the survival rate of mice.Compared with the model group,mice in the Angelica sinensis polysaccharide group showed a significant decrease in the ratio of Th1/Th2 cells(P<0.01),a decrease in the expression level of interferon-γ(P<0.01),an increase in the level of interleukin-4(P<0.05),a significant increase in the level of VEGFA(P<0.01),a significant decrease in EGLN1(P<0.01),a significant decrease in apoptosis rate of bone marrow single nucleated cells and reactive oxygen species level(P<0.01),and a significant increase in cleaved Caspase-3 protein expression(P<0.01),and a significant decrease in Bcl-2/Bax ratio(P<0.01).(5)These findings show that Angelica sinensis polysaccharide can improve hematopoiesis of aplastic anemia mice by regulating aberrant T-cell subsets and promoting angiogenesis to improve hematopoietic microenvironment,and inhibiting apoptosis of bone marrow mononuclear cells.

ObjectiveTo investigate the therapeutic effect of Scutellariae Radix-Coptidis Rhizoma （SRCR） on atherosclerosis （AS） in mice and the effect of SRCR on macrophage pyroptosis in plaques via NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasomes. MethodApoE^-/- mice were fed with a high-fat diet for the modeling of AS and randomized into model， atorvastatin （5 mg·kg^-1）， and low-， medium-， and high-dose （1.95， 3.9， 7.8 g·kg^-1， respectively） SRCR groups. Normal C57BL/6J mice were selected as the control group. After 8 weeks of administration， hematoxylin-eosin staining was used to observe the pathological status of the aortic plaque. The lipid accumulation in aortic plaque was observed by oil red O staining. The serum levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in mice were measured. Immunofluorescence double staining was employed to detect the co-localized expression of EGF-like module-containing mucin-like hormone receptor-like 1 （EMR1）/NLRP3 and EMR1/gasdermin D （GSDMD）. The serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1， cleaved Caspase-1， GSDMD， N-terminus of GSDMD （GSDMD-NT）， pro-IL-1β， IL-1β， and IL-18 were determined by Western blot， and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group showed obvious plaques， elevated serum levels of TG， TC， LDL-C， IL-1β， and IL-18 （P<0.01）， lowered serum level of HDL-C （P<0.01）， and up-regulated expression of NLRP3 inflammasomes and molecules related to pyroptosis in the aortic plaques （P<0.01）. Compared with the model group， SRCR， especially at the medium and high doses， alleviated the plaque pathology， reduced the lipid content in plaques （P<0.05， P<0.01）， recovered the serum lipid levels （P<0.05）， reduced the macrophage recruitment （P<0.01）， activation of NLRP3 inflammasomes， and pyroptosis in aortic root plaques （P<0.05）， lowered the serum IL-1β and IL-18 levels （P<0.01）， and down-regulated the protein levels of NLRP3， ASC， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-NT， pro-IL-1β， IL-1β， and IL-18 （P<0.05） and the mRNA levels of NLRP3， ASC， Caspase-1， GSDMD， IL-1β， and IL-18 in the aortic tissue （P<0.05）. ConclusionSRCR exerts a therapeutic effect on high-fat diet-induced AS in mice by inhibiting the activation NLRP3 inflammasomes and reducing the pyroptosis of macrophages in plaques.

Biological hydroxyapatite(BHA)is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity.The clinical application of mateiral size is based on the principle of bone defect area adaptation,which contributes to diversity of BHA sizes.However,different sizes correspond to different hierarchi-cal levels of bone biomimicry.As the size changes,the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation,leading to unstable bone graft outcomes.Therefore,this paper reviews the size effect of clinical BHA,analyzes the multilevel structure of natural bone,proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA,and further analyzes the size-media-ted osteo-coagulo-immunomodulation.Based on the hierarchical levels of bone and its osteo-coagulo-immunomodula-tion effect,we provide a new understanding of the biolog-ical principle of the size effect of biomaterials and a theo-retical basis for the basic research and clinical application of different size BHA materials.

ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic （AS） mice and to explore its possible mechanism of action based on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-κB） signaling pathway. MethodTen normal C57BL/6J mice were used as the normal group， and the same strain of ApoE knockout （ApoE^-/-） mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups， namely the model group， the atorvastatin group， and the Scutellariae Radix-Coptidis Rhizoma low-， medium-， and high-dose groups， with ten mice in each group. Then normal and model groups were given equal volume of saline gavage， and the low-， medium-， high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95， 3.9， 7.8 g·kg^-1 of the drug by gavage for 8 weeks， respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， TLR4， MyD88， NF-κB p65， and phosphorylation （p） -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） assay was employed to detect the expression levels of MMP-2， MMP-9， TLR4， and MyD88， NF-κB p65 mRNA. ResultCompared with the model group， the general state of the mice in each medication group was improved， and no obvious side effects were observed. Compared with the model group， the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased （P<0.01）， and the content of lipids and macrophages was significantly reduced （P<0.05）， the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced， with significant reduction of the medium- and high-dose groups （P<0.01）. MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups， the levels of TLR4， MyD88 protein， and mRNA expression in aortic tissues were significantly reduced （P<0.05）， and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced （P<0.05）. ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

The oral implant surgery robot could achieved basic "surgical operation intelligence"; however, "decision-making artificial intelligence" has not yet been achieved. The author previously discussed the specific concept of decision-making artificial intelligence. During our exploration of decision-making artificial intelligence, our team further integrated the clinical diagnosis and treatment process of oral implantation, along with the data characteristics of decision indicators and the distribution characteristics of demographic information. As a result, we identified five key scientific and technological issues in the process of decision-making artificial intelligence, namely the construction of a specialized annotation database for oral implantation, the prediction of quantitative indicators, the application of three-dimensional imaging, the solution of data imbalance within indicators, and the joint output of multi-property and multimodal indicators in clinical pathways. This paper will review artificial intelligence research in oral implantology and our team′s research progress, elaborating on the aforementioned challenges in intelligentization. It aims to provide references for addressing the mentioned scientific issues and guiding future research directions in the construction of decision-making artificial intelligence in oral medicine.

Objective To investigate the effect of Angelica polysaccharides on the balance of Th17/T-regulatory(Treg)cells and the expression of related inflammatory factor proteins in the bone marrow of mice with aplastic anemia.Methods 50 male BALB/c mice were randomly divided into a normal group,model group,cyclosporine A(CsA)group,and angelica polysaccharide low-(APS-L)and high-dose(APS-H)groups.A mouse model of aplastic anemia was prepared by combining irradiation with allogeneic lymphocyte infusion.After modeling,the mice were orally administered with corresponding drugs for 28 days.The general condition,weight changes,and spleen index of the mice were observed.Blood samples were taken to test for changes in basic hematological parameters of peripheral blood,and hematoxylin and eosin staining was used to evaluate the pathological changes in mouse bone marrow tissue.An ELISA method was applied to detect bone marrow TGF-β1.The expression levels of proteins such as IL-10,IL-17A,and IL-6 were analyzed,and flow cytometry was used in detecting the bone marrow Th17/Treg cell ratio.Results Compared with the normal group,the model group mice showed clumsiness during activity;lethargy;pale eyelids,lips,and ears;and reduced food and water intake.Both body weight and spleen index were significantly decreased.Peripheral red blood cell,white blood cell,and platelet counts and hemoglobin concentration were significantly reduced.A disordered bone marrow tissue structure and significantly reduced proliferation of hematopoietic tissue were seen.The expression of IL-17A and IL-6 proteins was significantly upregulated,and the expression of TGF-β1 and IL-10 protein was significantly downregulated.The proportion of Th17 cells in bone marrow significantly increased,the proportion of Treg cells significantly decreased,and the ratio of Th17/Treg cells significantly increased(P＜0.01).Compared with the model group,the general condition of the APS-L and APS-H groups improved,showing an increase in food and water intake;a significant increase in body weight and spleen index;a significant increase in peripheral red blood cells,white blood cells,platelets,and hemoglobin concentration(P＜0.05);an improvement in bone marrow tissue structure;and an increase in hematopoietic tissue proliferation(P＜0.05).The expression of IL-17A and IL-6 proteins was significantly downregulated.The expression of TGF-β1 and IL-10 protein was significantly upregulated(P＜0.05 or P＜0.01).The proportion of Th17 cells in bone marrow significantly decreased,the proportion of Treg cells significantly increased,and the ratio of Th17/Treg cells significantly decreased(P＜0.01).Conclusions Angelica polysaccharides can improve bone marrow hematopoietic function in aplastic anemia mice,and its mechanism of action may include the regulation of Th17/Treg cell balance.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

At present, implant surgery robots have basically achieved "surgical intelligence", but "brain-inspired intelligence" of robots is still in the stage of theory and exploration. The formulation of a clinical implantation plan depends on the timing of implantation, implantation area, bone condition, surgical procedure, patient factors, etc., which need to evaluate the corresponding clinical decision indicators and clinical pathways. Inspired by evidence-based medicine and the potential of big data and deep learning, combined with the data characteristics of clinical decision indicators and clinical pathways that can be quantitatively or qualitatively analyzed, this review simulates the cognitive behavior and neural mechanisms of the human brain and proposes a feasible brain-inspired intelligence scheme by predicting the decision indices and executing clinical pathways intelligently, that is, "select clinical indicators and clarify clinical pathways -- construct database -- use deep learning to intelligently predict decision indicators -- intelligent execution of clinical pathways -- brain-inspired intelligence of implant decision-making". Combined with the previous research results of our team, this review also describes the process of realization of brain-inspired intelligence for immediate implant timing decisions, providing an example of the comprehensive realization of brain-inspired intelligence of implant surgery robots in the future. In the future, how to excavate and summarize other clinical decision factors and select the best way to realize the automatic prediction of evidence-based clinical indicators and pathways and finally realize the complete intellectualization of clinical diagnosis and treatment processes will be one of the directions that dental clinicians need to strive for.

A good integration of dental implants and the surrounding soft tissue is essential to ensure the long-term effect of implant. In this review, we summarized the research progress of peri-implant soft tissue integration of dental titanium implants, with emphasis on the modification of the gingival interface of implants based on immune microenvironment regulation. This method influences the immune response around the implant by promoting the surface properties of implants, so as to enhance the peri-implant soft tissue integration. The purpose of this review is to provide reference for the related research and clinical application in the field of dental implantation.

Guided bone regeneration technology applied in alveolar bone defect regeneration is based on the barrier function and space maintenance of the barrier membrane. Therefore, traditional development strategies for barrier membranes focus on their physical barrier function, degradation characteristics and biocompatibility to avoid immunogenicity. However, not only does the barrier membrane passively block connective tissue, it is recognized as a “foreign body”that triggers a persistent host immune response, known as a foreign body reaction. The theories of osteoimmunology reveal a close relationship between the immune system and bone system and emphasize the role of immune cells in bone tissue-related pathophysiological processes. Based on these findings, we propose a novel development strategy for barrier membranes based on immune microenvironment regulation: by manipulating mechanical properties, surface properties and physiochemical properties, barrier membranes are endowed with an improved immunomodulation ability, which helps to regulate immune cell reactions to induce a favorable local immune microenvironment, thus coordinating osteogenesis and osteoclastogenesis as well as barrier membrane degradation to increase the efficiency of barrier membranes in GBR applications. In this paper, we review the development of barrier membranes and their close relationship to the immune microenvironment concerning bone regeneration and membrane degradation. Additionally, the outcomes of research on barrier membranes based on the regulation of the immune microenvironment have been summarized to improve the osteogenesis efficiency of barrier membranes and solve the problem of the regeneration and repair of bone defects, especially alveolar bone defects.