Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

OBJECTIVE: This study aimed to investigate the effect of Astragalus (AST) on osteoporosis (OP) and the downstream mechanisms. METHODS: Human bone marrow-derived mesenchymal stem cells (hBMSCs) were induced to differentiate into osteogenic cells. After transfection with relevant plasmids, cell proliferation, cell cycle progression, and apoptosis were assessed. Alizarin red staining was used to detect calcium nodules in the cells, alkaline phosphatase (ALP) staining was used to detect ALP activity in the cells, and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels. An OP rat model was established using ovariectomy and micro-computed tomography scanning. Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the pathological conditions of bone tissues, while immunohistochemistry was conducted to detect RUNX2 in bone tissues. RESULTS: AST promoted the osteogenic differentiation of BMSCs, reduced miR-181d-5p expression levels, and increased SOX11 expression levels. Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs. miR-181d-5p was found to target SOX11 in hBMSCs. AST improved OP in rats, and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats. CONCLUSION AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.
Osteogenesis/drug effects* ; Animals ; MicroRNAs/genetics* ; Mesenchymal Stem Cells/drug effects* ; Osteoporosis/drug therapy* ; Humans ; Cell Differentiation/drug effects* ; Astragalus Plant/chemistry* ; Rats ; Rats, Sprague-Dawley ; Female ; SOXC Transcription Factors/genetics* ; Plant Extracts/pharmacology* ; Cells, Cultured ; Drugs, Chinese Herbal/pharmacology*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective To investigate the effect and mechanism of M2 macrophage polarization induced by HCT116 with highly metastatic colorectal cancer cells on immune escape in colorectal cancer.Methods After the co-cul-ture of colorectal cancer cells conditioned medium(CM)and PMA-induced M0 macrophages,the polarization of M2 macrophages was observed by flow cytometry,real-time polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay(ELISA)experiments.The CMM0,CMSW480-Mφand CMHCT116-Mφ were co-cultured with HCT116 cells,and the expression of programmed death-ligand 1(PD-L1)was detected by Western blot and qPCR.At the same time,the stimulated HCT116 cells were co-cultured with human T lymphocytes to detect the survival of HCT116 cells and the levels of tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).The difference of kruüppel-like factor 4(KLF4)expression between SW480 and HCT116 cells was detected by Western blots,qPCR and ELISA.After pretreatment of HCT116 cells with KFL4 inhibitor Kenpaullone(Ken),the CMHCT116 and CMHCT116+Ken were co-cultured with M0 macrophages and the polarization of M2 macrophages was observed by flow cytometry,qPCR and ELISA.The CMHCT116-Mφ and CM(HCT116+Ken)-Mφ was co-cultured with HCT116 cells,and the PD-L1 expression of HCT116 cells was detected by Western blot and qPCR.Results After the stimulation of M0 macrophages with CM,the proportion of CD11b+CD206+cells in HCT116-Mφ cells was higher,and the expres-sion of M2 macrophage markers interleukin(IL-10)and transforming growth factor-β(TGF-β)were higher.Com-pared with the CMSW480-Mφ group,the PD-L1 protein expression level was higher in the CMHCT116-Mφ group.After co-culture with T lymphocytes,the cell survival rate are the most in CMHCT116-Mφ group,while the levels of TNF-α and IFN-γ were the lowest.After the addition of Ken,the polarization ratio and markers of M2 macrophages decreased.Compared with CMHCT116-Mφ group,the expression of PD-L1 in HCT116 cells of the CM(HCT116+Ken)-Mφ group de-creased.Conclusion Highly metastatic colorectal cancer cells induce polarization of M2 macrophages by secreting KLF4,promote PD-L1 expression in colorectal cancer cells,facilitate tumor immune escape,and provide potential targets for clinical immunotherapy.

Objective:To explore the effect of exosomes released by Mycobacterium tuberculosis ( Mtb) Rv1983-stimulated macrophages on tuberculosis infection and its potential mechanism. Methods:Exosomes (Rv1983-M-Exo) released by macrophages following Mtb Rv1983 stimulation were extracted by hypervelocity centrifugation and then co-cultured with uninfected macrophages. Macrophage activity was detected by prodium iodide (PI) staining. The level of lipid reactive oxygen species (ROS) was detected by lipid peroxidation fluorescence probe. The expression of ferrous ions (Fe 2+ ) and malondialdehyde (MDA) were detected by colorimetry assay. The protein expression of acyl-CoA synthetase long chain family member 4 (ACSL4) in Rv1983-M-Exo was detected by Western blot. Exosomes (Rv1983-M+ siACSL4-Exo) were isolated from Rv1983-stimulated macrophages with interfered ACSL4 expression Rv1983 and co-cultured with uninfected macrophages. The effect of exosomes on the polarization of macrophages was detected by flow cytometry and Western blot. The effects of exosomes on phagocytosis and killing ability of macrophages were analyzed by plate colony assay and BCG-phagocytosis lysosome co-localization assay. Results:Compared with macrophage-derived exosomes (M-Exo), Rv1983-M-Exo promoted ferroptosis in uninfected macrophages, manifested by increased levels of intracellular lipid ROS, MDA and Fe 2+, which were significantly inhibited by ferroptosis inhibitor Fer-1. Rv1983 induced macrophages to release exosomes with high expression of ACSL4. Interfering the expression of ACSL4 in macrophages, the concentration of ACSL4 in the Rv1983-M+ siACSL4-Exo was significantly reduced. When the Rv1983-M+ siACSL4-Exo was co-cultured with uninfected macrophages, the ferroptosis of macrophages was significantly reduced. Rv1983-M-Exo promoted M2 macrophage polarization which showed up-regulation of CD206 and Arg1 expression, and decreased the phagocytosis and killing ability of macrophages, while Rv1983-M+ siACSL4-Exo or Fer-1 in combination with Rv1983-M-Exo reduced the expression of CD206 and Arg1 in macrophages, and promoted the phagocytosis and killing ability. Conclusions:Mtb Rv1983 protein up-regulates the level of ACSL4 in the exosomes secreted by macrophages, thereby inducing ferroptosis in uninfected macrophages, causing M2 polarization of macrophages, weakening phagocytosis and killing ability, and promoting Mtb infection.

Tardive dyskinesia (TD) is a medication-induced hyperkinetic movement disorder, generally manifested as involuntary spasms or choreiform movements of the tongue, lower face and jaw, and limbs (lasting at least several weeks). It occurs after using neuroleptic medication for at least several months, causing irreversible injuries to the nerve system and significantly impacting patients′ daily function. This review summarizes recent research progress regarding TD risk factors, possible pathogenesis, clinical characteristics, assessment and identification, and treatment and management approaches. The goal is to raise awareness of TD to archive early prevention and identification, standardize treatment, and improve patients′ prognosis and quality of life.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Wnt signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer bibliometric software,the literature on the regulation of Wnt signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results As of April 2023,607 and 257 related literatures were published in Chinese and English respectively.Since 2008,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;guangzhou University of Traditional Chinese Medicine and Hunan University of Traditional Chinese Medicine were the institutions with the most publications in the Chinese database,and Shanghai University of Traditional Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Wnt signaling pathway are focused on osteoporosis,osteoarthritis and renal fibrosis.Diseases such as gastric cancer and breast cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.The mechanism of traditional Chinese medicine regulating the interaction between Wnt and NF-kappaB signaling pathway to prevent and treat diseases has great research potential.Conclusion In recent years,the prevention and treatment of diseases by traditional Chinese medicine targeting Wnt signaling pathway has developed rapidly.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.