BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition.OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques.METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes.RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.

BACKGROUND:Recent studies have shown that the Notch signaling pathway plays a varying role in osteoporosis,and in-depth research in this field is of great significance to the prevention and treatment of osteoporosis.Traditional Chinese medicine has become the focus of research in today's society due to its obvious multi-faceted,multi-level benefits in alleviating osteoporosis with less adverse effects. OBJECTIVE:To analyze and summarize domestic and international literature to further understand the connection between the Notch signaling pathway and osteoporosis and to elucidate the mechanism by which traditional Chinese medicine prevents and treats osteoporosis via the Notch signaling pathway. METHODS:CNKI,WanFang,and VIP were searched with the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathway,traditional Chinese medicine,pill,experiment"in Chinese.PubMed,Nature,and Embase were retrieved using the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,mesenchymal stem cells,signal pathway,traditional Chinese medicine,pill,experiment"in English.The search time was from database inception to October 2022. RESULTS AND CONCLUSION:The Notch signaling pathway plays a role in the development and progression of osteoporosis to varying degrees by regulating the differentiation and proliferation of mesenchymal stem cells,osteoblasts and osteoclasts.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,osteoblasts and osteoclasts by directly or indirectly regulating key cytokines such as Notch1,Jagged1,Hes,Hey,macrophage colony-stimulating factor and nuclear factor-κB receptor-activating factor ligand,which in turn promotes or inhibits bone formation and ultimately has a certain effect on the prevention and treatment of osteoporosis.The active ingredients of Chinese herbs are mostly extracted from herbs for kidney tonifying,such as Epimedium,Cortex Eucommiae,Malaytea Scurfpea Fruit,Eleutherococcus Senticosus,Ligustrum Lucidum.Moreover,herbal compounds and preparations have the effect of tonifying kidney and strengthening bone,which provides more herbal options and directions for the subsequent study of Notch signaling pathway toward the prevention and treatment of osteoporosis.Current studies on traditional Chinese medicine mainly focus on active ingredients and single herbal extracts,with relatively few clinical trials on Chinese herbal compounds and preparations.Fewer studies have been conducted on the regulation of Notch signaling pathways by acupuncture,manipulation,and integrated Chinese and Western medicine to prevent and treat osteoporosis.Therefore,there is a need to explore the mechanisms by which traditional Chinese medicine technology-based therapies and integrated Chinese and Western medicine regulate the Notch signaling pathway to treat osteoporosis.

BACKGROUND:The nuclear factor-κB signaling pathway plays an important role in the pathogenesis of osteoporosis.In recent years,increasing studies have shown that terpenoid herbal monomer compounds can inhibit the activity of bone resorbing cells and promote the differentiation of bone forming cells via the nuclear factor-κB signaling pathway,thus reducing bone resorption and increasing bone formation,which has certain preventive and therapeutic effects on osteoporosis. OBJECTIVE:By analyzing and summarizing the domestic and international literature,to investigate the relationship between nuclear factor-κB signaling pathway and osteoporosis in depth,elucidate the mechanism of terpenoid monomer compounds in regulating the nuclear factor-κB signaling pathway to prevent osteoporosis,and systematically summarize the terpenoid monomer compounds targeting to regulate the nuclear factor-κB signaling pathway to prevent osteoporosis. METHODS:According to the proposed inclusion and exclusion criteria,two researchers searched for relevant articles published from database inception to December 2022 in CNKI and PubMed using the search terms"NF-κB,osteoporosis,osteoblasts,osteoclasts,angiogenesis,traditional Chinese medicine,terpenoid"in Chinese and English,respectively.A third researcher summarized and organized the literature and 75 articles were finally included for a systematic review. RESULTS AND CONCLUSION:The nuclear factor-κB signaling pathway mediates the onset and progression of osteoporosis by regulating the differentiation and proliferation of osteoblasts and osteoclasts,as well as angiogenesis.Activation of the nuclear factor-κB signaling pathway negatively regulates the proliferation and differentiation of osteoblasts.Activation of the nuclear factor-κB signaling pathway enhances osteoclast activity and inhibits osteoblast growth,thereby inhibiting compensatory bone production to maintain bone homeostasis.However,over-activation of the nuclear factor-κB signaling pathway can lead to osteoporosis.The nuclear factor-κB signaling pathway is involved in the"angiogenesis-osteogenesis"coupling by upregulating the expression levels of cytokines such as angiopoietin-1,platelet-derived growth factor BB and vascular endothelial growth factor,which promote the growth of blood vessels in bone.The terpenoid herbal monomer compounds are used in the field of tissue engineering to promote the proliferation and differentiation of bone cells,thereby promoting the growth and repair of bone tissue.Terpenoid herbal monomer compounds can prevent and treat osteoporosis by inhibiting the degradation of nuclear factor-κB inhibitor,blocking nuclear factor-κB/p65 phosphorylation and nuclear translocation,thereby weakening the nuclear factor-κB signaling pathway,promoting osteoblast differentiation and inhibiting osteoclast formation.Currently,research on the regulation of nuclear factor-κB signaling pathway by monomeric compounds of terpenoids to prevent osteoporosis is mainly based on in vitro cellular experiments and animal models,and there is a lack of research on the complex physiological and pathological processes in humans.In the future,more clinical trials and studies are needed to further clarify the mechanism of action and efficacy of the nuclear factor-κB signaling pathway involved in the intervention of osteoporosis.

Objective To investigate the risk factors for recurrence of persistent atrial fibrillation(AF)after radiofrequency ablation with circumferential pulmonary vein isolation+top line+back wall line based on the features of cardiac imaging and serum biomarkers,and then to establish a nomogram risk prediction model.Methods A total of 172 patients with persistent AF admitted to our hospital from June 2022 to September 2023 were enrolled and then according to recurrence or not in 6 months after surgery,they were divided into the recurrence group(51 cases)and the non-ecurrence group(121 cases).Before surgery,routine electrocardiography,and transthoracic and esophageal echocardiography were performed,while blood routine indicators and related biochemi-cal indicators were measured.All patients underwent radiofrequency ablation with circumferential pulmonary vein isolation,top line,and back wall line.They were followed up for 6 months after surgery.Binary logistic analysis was used to analyze the independent risk factors for postoperative recurrence,and then a nomogram risk prediction model was constructed and its diagnostic per-formance was evaluated.Results Lager LAD,higher LAVI,neutrophil count and NLR,and ele-vated BNP and CRP levels,while lower LAAFV,LAAEV and LAAEF were observed in the re-current group than those in the non-recurrent group(P＜0.01).Binary logistic regression analysis showed that elevated LAVI(OR=1.160,95％CI:1.006-1.337),decreased LAAEV(OR=0.740,95％CI:0.583-0.940),decreased LAAEF(OR=0.608,95％CI:0.422-0.877),elevated BNP(OR=1.017,95％CI:1.004-1.030),and higher NLR(OR=10.116,95％CI:1.316-77.755)were independent risk factors for recurrence after radiofrequency ablation of pulmonary vein isolation+top line+posterior wall line in persistent AF patients(P＜0.05,P＜0.01).The AUC value of the nomogram model constructed with LAVI,LAAEV,LAAEF,BNP and NLR in predicting postop-erative recurrence was 0.889(95％CI:0.833-0.932).Conclusion The cardiac imaging parame-ters LAVI,LAAEV and LAAEF,and serum biomarkers BNP and NLR are closely associated with postoperative recurrence of persistent AF in patients after radiofrequency ablation with cir-cumferential pulmonary vein isolation+top line+back wall line,and the relevant nomogram mod-el has better diagnostic value for postoperative recurrence.

Objective To explore the research hotspots and development trend on vascular dizziness/vertigo based on visual analysis. Methods The Web of Science Core Collection Database was searched for papers on vascular dizziness/vertigo from January 2008 to March 2023. The CiteSpace 6.2.R2 software was used for visual analysis of the literature. Results There were a total of 1298 papers，with an increasing number of published papers from January 2008 to March 2023. A total of 424 institutions from 83 countries/regions had published relevant papers. The United States ranked first in terms of the number of published papers（331 papers） and betweenness centrality（0.25）. Johns Hopkins University was the number one institution in terms of the number of published papers （56 papers），Newman-toker and David E were the most prolific authors. The most common keyword was ischemic stroke. According to keyword clustering，research in this field focused on early diagnosis of vascular dizziness/vertigo from risk factors and bedside examinations and infarction of the anterior inferior cerebellar artery supply area. In recent years，researchers had more interests in case reports，video electronystagmograms，and pathophysiological mechanisms in this field. Conclusion There are growing international studies on vascular dizziness/vertigo. Early diagnosis of vascular dizziness/vertigo through risk factors and bedside examinations in the emergency room is a research hotspot in this field. Researchers should focus on these topics in future studies.

Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.