ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

BACKGROUND:The accurate diagnosis of early bone metastases plays an important role in treatment and prognosis.Bone biopsy is the gold standard for the diagnosis of bone metastases,but it is difficult to implement in clinical practice because of its invasive and small specimen size.In recent years,with the continuous development of magnetic resonance imaging technology,quantitative magnetic resonance imaging techniques such as magnetic resonance spectroscopy and based on chemical shift encoded magnetic resonance imaging have been widely used in the diagnosis of bone metastasis.The derived markers include table signal fat fraction and proton density fat fraction.All of them could reflect the bone marrow fat content.At present,the role of bone marrow fat in the development of bone metastases has become a new focus of attention. OBJECTIVE:To review the effect of bone marrow fat on bone metastasis and the quantitative evaluation techniques of magnetic resonance imaging,to summarize and compare the advantages and disadvantages of different magnetic resonance imaging fat quantification techniques in evaluating bone metastasis and their clinical applications. METHODS:The computer was used to search relevant literature in PubMed and CNKI database.Chinese and English search terms were"bone metastases,bone marrow adipocytes,magnetic resonance imaging,quantitative MRI,fat fraction,magnetic resonance spectrum,chemical shift encoding-based water-fat imaging."A total of 67 relevant articles were obtained according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Bone marrow adipocytes can contribute to the occurrence of bone metastasis by secreting a variety of related hormones and cytokines,providing energy for tumor cells,and inducing osteoclast differentiation.(2)Quantitative magnetic resonance imaging can accurately quantify adipose tissue and measure the change of fat content in bone marrow,which is helpful for the diagnosis of bone metastasis.(3)Magnetic resonance spectroscopy can reflect different metabolites through different proton precession frequencies,so it can be used for fat quantification,and is currently used as an auxiliary test to evaluate metastatic fractures.(4)Chemical shift encoding-based water-fat imaging can separate water and fat signals in positive and inverse phases,so as to measure adipose tissue signals,with high sensitivity,specificity and accuracy in differentiating benign and malignant vertebral fractures.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

BACKGROUND:As the end bearing joint of the human body,the ankle joint bears the top-down pressure of the body,which leads to the ankle joint is easy to be damaged in the movement,can induce functional ankle instability,which negatively affects daily life.The study of lower extremity biomechanics in patients with functional ankle instability during counter movement jump is of great significance for scientific training,prevention of ankle injury,and clinical rehabilitation after injury. OBJECTIVE:To investigate the kinetics and kinematics of lower limbs in the longitudinal jumping of functional ankle instability population. METHODS:From March to September 2023,15 male patients with functional ankle instability and 15 healthy people,aged 22-28 years old,were recruited in Soochow University.All subjects completed counter movement jump experiment.Vicon infrared high-speed motion capture system and Kistler three-dimensional force measuring table were used to simultaneously collect the lower limb kinematics and kinetics indexes of the two groups of subjects at the take-off stage of counter movement jump,the instant off the ground,the initial landing moment and the peak moment of vertical ground reaction force. RESULTS AND CONCLUSION:(1)At the instant off the ground,the affected side of the functional ankle instability group showed smaller knee internal rotation moment(P=0.020)and smaller ankle internal rotation moment(P=0.009)compared with the affected side of the healthy control group.(2)At the moment of landing,the affected side of the functional ankle instability group showed a smaller hip flexion angle than the affected side of the healthy control group(P=0.039).Compared with the healthy control group,functional ankle instability group showed smaller hip abduction angle(P=0.022),smaller knee varus angle(P=0.010),larger knee external rotation angle(P=0.021),smaller ankle varus angle(P=0.004),and smaller external ankle rotation angle(P=0.008).(3)At the peak of vertical ground reaction force,functional ankle instability group showed a smaller ankle varus angle than healthy control group(P=0.044).(4)The results showed that the lower limb biomechanical characteristics of the patients with functional ankle instability were abnormal compared with the healthy people during counter movement jump,which mainly showed the changes of the kinematics and kinetics indexes of the lower limb joints in the sagittal plane and the frontal plane at the moment of lift-off and landing.These changes reflect that people with functional ankle instability adopt rigid take-off and landing patterns when performing counter movement jump,tend to transfer the load of the affected ankle joint to other joints of the lower limb,and show compensatory phenomenon of the healthy lower limb.Therefore,detection and correction of abnormal biomechanical features should be a part of rehabilitation training for those with functional ankle instability.

BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

BACKGROUND:Stem cells can promote nerve regeneration,repair damaged nerves,inhibit inflammation and apoptosis of nerve cells,and provide a new way for the treatment of Alzheimer's disease. OBJECTIVE:To make a bibliometrical analysis of the articles on stem cell therapy for Alzheimer's disease published internationally from 2004 to 2023,in order to reveal the research hotspot and trend of stem cell therapy for Alzheimer's disease. METHODS:From the Web of Science Core Collection database,by using Excel,VOSviewer,and Citespace software,the annual number of publications,countries,institutions,journals/co-cited journals,authors,and keywords of articles related to stem cells and Alzheimer's disease published from January 1,2004 to October 31,2023 were visually analyzed. RESULTS AND CONCLUSION:A total of 3 521 core papers were included,and the number of published papers increased year by year.The United States is the country with the most papers.Harvard Medical School is the most prolific institution.Maiese kenneth is the author with the most papers.International Journal of Molecular Sciences has the most papers in this field.The journal PLoS One published the most citations.At present,the field of stem cell therapy for Alzheimer's disease focuses on pathophysiological mechanism and animal experimental research,and"neurogenesis","oxidative stress","extracellular vesicles",and"mesenchymal stem cells"are the research trends in this field.Stem cell therapy for Alzheimer's disease has broad prospects.In the future,exchanges and cooperation between institutions and authors should be strengthened to further explore the main mechanism of stem cell therapy for Alzheimer's disease,solve possible clinical problems such as immune rejection,effectiveness,and safety,and further tap the potential of stem cells in the treatment of Alzheimer's disease.

OBJECTIVE:The optimal non-surgical therapy for chronic ankle instability remains unclear due to the continuous introduction of novel treatment methods despite the availability of several non-surgical options for improving foot and ankle function and dynamic balance in chronic ankle instability patients.This study aims to investigate the most effective non-surgical therapy options to improve foot and ankle function and dynamic balance for patients with chronic ankle instability using a network meta-analysis. METHODS:Using"CAI,exercise,and randomized controlled trial"as search terms,a literature search of PubMed,Embase,Cochrane Library,and Web of Science databases was conducted through a computer network to collect information from the databases from their inception to March 2024 on non-surgical therapies for the treatment of chronic ankle instability randomized controlled trials on foot and ankle function or dynamic balance in patients.EndNote software was utilized for literature management.RevMan 5.4 software and Cochrane Risk of Bias Assessment Tool were used to evaluate the risk of bias of the included literature.Paired meta-analysis and network meta-analysis of the outcomes such as the Foot and Ankle Ability Measure in daily living subscale score,Foot and Ankle Ability Measure in sports activities subscale score,Star Excursion Balance Test-Anterior score,Star Excursion Balance Test-Posteromedial score,Star Excursion Balance Test-Posterolateral score and Cumberland ankle instability tool score were performed using the network commands of Stata 14.0 software.The strength of evidence rating of the outcome metrics was evaluated according to the GRADE Level of Evidence and Strength of Recommendation Grading Criteria. RESULTS:Of the 22 randomized controlled trials that met the inclusion criteria,1 study was rated as low risk,8 studies were rated as medium risk,and 13 studies were rated as high risk,enrolling a total of 952 patients and 25 treatments.(1)Network meta-analysis showed that compared with the control group,Isokinetic Strength Training,Balance Training,Balance+Stroboscopic Glasses Training,Strength Training,Joint Mobilizations Training,CrossFit Training,CrossFit Training+Self-Mobilization,Wobble Board Training,National Academy of Sport Medicine corrective exercise program,Trigger Point Dry Needling,and Neuromuscular Training had different significant enhancement effects on improving foot and ankle function and dynamic balance in patients with chronic ankle instability(P<0.05).(2)Cumulative probability ranking results showed that the three treatments with the highest ranked Cumberland ankle instability tool score were Joint Mobilizations Training(88.6%)>Visual Feedback Balance Training(83.1%)>CrossFit Training+Self-Mobilization(74.8%);the three treatments with the highest ranked Star Excursion Balance Test-Anterior score were Joint Mobilizations Training(88.4%)>Isokinetic Strength Training(86.9%)>National Academy of Sport Medicine corrective exercise program(65.0%);the three treatments with the highest ranked Star Excursion Balance Test-Posteromedial score were Balance+Stroboscopic Glasses Training(87.4%)>Neuromuscular Training(74.6%)>Strength Training(68.9%);the three treatments with the highest ranked Star Excursion Balance Test-Posterolateral score were CrossFit Training+Self-Mobilization(74.6%)>Balance+Stroboscopic Glasses Training(70.0%)>Neuromuscular Training(63.7%);the three treatments with the highest ranked Foot and Ankle Ability Measure in daily living subscale score were National Academy of Sport Medicine corrective exercise program(91.9%)>Balance+Stroboscopic Glasses Training(85.6%)>Wobble Board Training(82.2%);the three treatments with the highest ranked Foot and Ankle Ability Measure in sports activities subscale score were Balance+Stroboscopic Glasses Training(93.5%)>Balance Training(86.7%)>National Academy of Sport Medicine corrective exercise program(86.4%). CONCLUSION:Non-surgical therapies can significantly improve foot and ankle function and dynamic balance in patients with chronic ankle instability.National Academy of Sport Medicine corrective exercise program had the best efficacy in improving foot and ankle daily activity function in chronic ankle instability patients;Balance+Stroboscopic Glasses Training had the best efficacy in improving foot and ankle sports function and posterior medial dynamic balance;Joint Mobilizations Training had the best efficacy in improving anterolateral dynamic balance and ankle instability condition;and CrossFit Training+Self-Mobilization had the best efficacy in improving posterior lateral dynamic balance.The strength of evidence for each outcome was low,influenced by the risk of methodological bias and risk of publication bias of the included studies.Therefore,the above conclusions need to be validated by more high-quality pilot studies.

BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 （NLRP3） inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3， apoptosis-associated speck-like protein ， containing a CARD （ASC）， and caspase-1 precursor （pro- No.20-21ZY1053） caspase-1） were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group， model group， dexamethasone group （0.002 g/kg）， and Pangshi antai zhixue decoction low-， medium-， and high-dose groups （11.025， 22.05， 44.10 g/kg）， with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically， once a day， for 12 consecutive days. Except for normal group， other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication， serum levels of triiodothyronine （T3）， thyroxine （T4）， interleukin-2 （IL-2）， IL-4， IL-6， IL-10， and interferon-γ （IFN-γ） were all detected； the abortion rate and uterine coefficient were calculated； the pathological morphology of the pregnant uterus was observed； protein expressions of NLRP3， ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3， ASC， and pro-caspase-1 were all less than －5 kJ/moL. The animal experiment results showed that compared with normal group， the uterine coefficient and serum levels of IL-4， IL-6 and IL-10 were decreased significantly in model group （P＜0.05）； the abortion rate and serum levels of T3， T4， IL-2 and IFN-γ as well as protein expressions of NLRP3， ASC and caspase-1 were increased significantly （P＜0.05）； there were abortion lesions in the pregnant endometrium. Compared with the model group， most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups （P＜0.05）， and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome， down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2， and up-regulating anti-inflammatory cytokines such as IL-4， IL-6 and IL-10， thereby improving spontaneous abortion with heat syndrome.