BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Living microecological hydrogels are a hot topic in the field of wound dressing and have received widespread attention.OBJECTIVE:To summarize the basic features and advantages of living microecological hydrogels,review the progress in the application of hydrogels loaded with different living organisms in skin wound repair in recent years.METHODS:The articles published from database inception to 2024 were retrieved from Web of Science,PubMed,CNKI,and WanFang databases with"cell,probiotics,phage,chlorella,algae,living microecological,hydrogel,skin,wound healing,wound repair"as search terms in English and Chinese.The articles for inclusion were screened according to the inclusion and exclusion criteria.Finally,108 articles were included for review.RESULTS AND CONCLUSION:The living microecological hydrogels have good biocompatibility,and the hydrogel can provide a suitable living environment for the loaded organisms,and play a barrier role between the living organisms and the wound to avoid potential threats.Compared with traditional wound dressings,the effect of living microecological hydrogels is sustainable and renewable.Biological regulation can keep the microenvironment at the wound site relatively stable,which can provide suitable conditions for wound healing for a long time and reduce the additional trauma caused by frequent dressing changes.Compared with the direct use of living organisms to promote wound healing,living microecological hydrogels can improve the survival rate of organisms and ensure their biological regulation.Living microecological hydrogels promote wound healing mainly by regulating the"inflammation"and"proliferation"stages in the wound healing process.The existing living microecological hydrogels mainly load organisms such as cells,probiotics,algae,and phages,which give hydrogels with different biological properties,so that they can promote wound healing by releasing substances required for wound healing or improving the wound environment,and have great application potential.To further expand the actual clinical application of living microecological hydrogels,it is necessary to further control the biosafety risks of active organisms in hydrogels in the future,avoid potential biological threats,and research the hydrogel matrix that can better adapt to the complex changes of human skin wounds and can support living organisms.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.

BACKGROUND:Mitochondrial dysfunction is a key mechanism underlying the pathogenesis and progression of diabetic cystopathy.Recent studies have suggested that drugs targeting mitochondrial metabolism,oxidative stress,and apoptosis pathways can inhibit bladder tissue degeneration,offering novel therapeutic directions for diabetic cystopathy.OBJECTIVE:To explore the association between mitochondrial abnormalities and diabetic cystopathy and to summarize the mechanisms of pharmacological interventions targeting mitochondrial function.METHODS:The key words are"mitochondria,diabetes,diabetic cystopathy,diabetic bladder dysfunction,detrusor,urothelium,neuron,peripheral nerves"in Chinese and English.Relevant literature was retrieved from CNKI,WanFang,PubMed,and Web of Science.Selected articles were systematically screened and analyzed.RESULTS AND CONCLUSION:During the progression of diabetic cystopathy,mitochondria in detrusor muscle,urothelium,and peripheral nerve cells exhibit alterations in characterization,activity,function,and behavior.Under diabetic conditions,mitochondrial damage leads to increased reactive oxygen species production,increased cytochrome C release,reduced Bcl-2/Bax ratio,enhanced nuclear translocation of apoptosis-inducing factors,and activation of the poly(ADP-ribose)polymerase/c-Jun N-terminal kinase/mitochondrial apoptosis pathway.Mitochondria also act as damage-associated molecular patterns to regulate NLRP3,triggering inflammatory responses.Disrupted mitochondrial energy metabolism involves AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1α signaling axis-mediated phenotypic changes,decreased levels of respiratory chain complexes Ⅰ,Ⅱ,andⅣ,impaired oxidative phosphorylation,inhibited tricarboxylic acid cycle,and reduced mitochondrial spare respiratory capacity.Novel therapeutic agents or formulations can ameliorate diabetic cystopathy by alleviating oxidative stress,exerting anti-inflammatory effects,and modulating energy-sensing pathways to restore mitochondrial function.Although mitochondrial roles in other diabetic complications have been extensively studied,research on their involvement in diabetic cystopathy remains insufficient and warrants further exploration.

BACKGROUND:The prevalence of osteoporosis is high in postmenopausal women,but muscle mass,grip strength,and how these factors affect osteoporosis are understudied,and the exact link between them has not been clarified.OBJECTIVE:To investigate the correlation between muscle mass,grip strength,appendicular skeletal muscle index and bone mineral density in postmenopausal women with osteoporosis and to assess the potential values of these indices in predicting and diagnosing postmenopausal osteoporosis.METHODS:Eighty-three postmenopausal women were collected from the outpatient clinic of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from February 2023 to January 2024.General data were collected.Bone mineral density was detected.T-value,muscle mass of each part,grip strength were recorded.The body mass index and appendicular skeletal muscle index were calculated.The patients were categorized into non-osteoporosis group(n=17)and postmenopausal osteoporosis group(n=66)according to T value and fracture history,and were statistically analyzed accordingly.RESULTS AND CONCLUSION:(1)The body mass,body mass index,bone mineral density of the overall lumbar spine,muscle mass and appendicular skeletal muscle index were higher in the non-osteoporosis group than the osteoporosis group(P＜0.05).(2)Muscle mass was positively correlated with bone mineral density of the overall lumbar spine and individual vertebrae(P＜0.05).(3)Multiple stepwise linear regression analysis showed that body mass and grip strength were linearly and positively correlated with muscle mass;body height and muscle mass were linearly and positively correlated with grip strength,and body mass was linearly and negatively correlated with grip strength.Body mass index was linearly and positively correlated with bone mineral density,and age was linearly and negatively correlated with bone mineral density.(4)Analysis by receiver operating characteristic curve showed that:muscle mass(the area under the curve,sensitivity,specificity and critical value of muscle mass were 0.744,76.50％,74.20％and 36.50 kg,respectively,with P=0.002)and appendicular skeletal muscle index(the area under the curve,sensitivity,specificity and critical value of appendicular skeletal muscle index were 0.739,82.40％,62.10％and 5.81 kg/m2,respectively,and P=0.002)had good predictive value for postmenopausal osteoporosis.To conclude,a reduction in muscle mass and appendicular skeletal muscle index can help to predict the risk of postmenopausal osteoporosis,and the possibility of osteoporosis should be taken into account in postmenopausal women when muscle mass is＜36.50 kg or appendicular skeletal muscle index is＜5.81 kg/m2,in order to prevent the occurrence of postmenopausal osteoporosis.

BACKGROUND:Dyslipidemia affects chondrocyte metabolism and plays an important role in the occurrence and progression of osteoarthritis,yet its underlying mechanisms remain unclear.OBJECTIVE:To identify characteristic genes related to lipid metabolism in chondrocytes of osteoarthritis through the weighted gene co-expression network analysis combined with machine learning algorithms and to conduct the preliminary experimental validation.METHODS:Based on the weighted gene co-expression network analysis and linear models for microarray data,differentially co-expressed genes were identified.Machine learning methods were used for screening characteristic genes related to lipid metabolism.Protein-protein interaction analysis was conducted to explore the interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the signaling pathways involved in the differentially co-expressed genes.Subsequently,immune correlation analysis was utilized to identify the associations between the characteristic genes and immune infiltration patterns.Furthermore,in vitro molecular experiments were performed to validate the mRNA and protein levels of the characteristic genes.RESULTS AND CONCLUSION:(1)A total of 123 high-expression and 110 low-expression differentially co-expressed genes were identified after data normalization and application of principal component analysis,weighted gene co-expression network analysis,and linear models for microarray data.(2)Thirty-seven characteristic genes were screened using logistic regression,random forest,and support vector machine,among which SMPD3 and CYP4F3 were identified as two characteristic genes related to lipid metabolism.(3)Protein-protein interaction analysis revealed that SMPD3 and CYP4F3 proteins showed relatively low levels of interaction.(4)Gene Ontology analysis indicated that these genes were primarily enriched in multiple biological processes,including neutrophils and their immune responses,immune system processes,and neutrophil activation.Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that they were mainly involved in key pathways such as extracellular matrix-receptor interaction and cell adhesion.(5)Cell type Identification by estimating relative subsets of RNA transcripts immune infiltration analysis showed significant differences in eight types of immune cells in osteoarthritis.Further correlation analysis revealed that SMPD3 was significantly positively correlated with resting dendritic cells(r=0.44,P=3.6×10-3)and significantly negatively correlated with neutrophils(r=-0.48,P=1.7×10-3),whereas CYP4F3 was significantly positively correlated with monocytes and neutrophils(r=0.76,P=7.6×10-9;r=0.73,P=6.0×10-8),and significantly negatively correlated with T follicular helper cells and resting dendritic cells(r=-0.38,P=0.01;r=-0.38,P=0.01).(6)In vitro molecular experiments demonstrated that SMPD3 mRNA and protein levels were significantly increased in the osteoarthritis group,while CYP4F3 mRNA and protein levels were decreased.To conclude,the lipid metabolism-related SMPD3 and CYP4F3 of osteoarthritis can serve as potential biomarkers for the targeted therapy of osteoarthritis and for assessing cartilage repair or degeneration,which provides a new strategy for exploring the relationship between dyslipidemia and osteoarthritis and for clinical targeted treatment in Chinese population.