BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.

BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

Objective: To analyze the associations of physical activity with overweight/obesity, depressive symptoms, and their co-occurrence among junior and senior high school students, so as to provide reference for optimizing physical activity intervention strategies and promoting healthy lifestyles. Methods: From March to November 2023, a cross sectional survey was conducted among 90 457 junior and senior high school students aged 11-18 years in Zhejiang Province using a stratified cluster random sampling method. Data on physical activity and dietary behavior were collected through questionnaires, height and weight were measured. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The Chi-square test was used to examine differences, and Logistic regression was applied to evaluate the associations of physical activity characteristics with overweight/obesity, depressive symptoms, and their co-occurrence. Additionally, the effectiveness of physical activity performed on rest days versus work days was examined. Results: The prevalence of overweight/obesity, depressive symptoms, and their co-occurrence among junior and senior high school students were 25.1%, 27.9%, and 6.7%, respectively, with significant sex differences ( χ 2=2 005.3, 587.7, 99.6, all P <0.01). Logistic regression analysis showed that students with insufficient physical activity had a higher risk of overweight/obesity compared with those with sufficient physical activity ( OR=1.12, 95%CI=1.06-1.17, P <0.01). Comparing to students who exercised 0-1 day per week, those who exercised 5-7 days per week were associated with a reduced risk of overweight/obesity and depressive symptoms ( OR=0.93, 95%CI =0.90-0.97; OR=0.95, 95%CI =0.91-0.99, both P <0.05). When total activity volume and frequency were held constant, students with sufficient rest day physical activity had lower risks of overweight/obesity, depressive symptoms, and their co-occurrence than those with insufficient rest day activity (all P < 0.01). Conclusions Sufficient amount of physical activity and higher frequency of rest day physical activity are significantly associated with lower risks of overweight/obesity, depressive symptoms, and their co-occurrence in adolescents. Physical activity performed on rest days may confer greater health benefits than activity performed on work days.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

Objective To implement the disease prevention and control strategy of being ^"proactive and grassroots-focused,^" and to enhance the overall effectiveness of general hospitals in the tertiary prevention of cervical cancer, this consensus aims to provide an actionable guiding framework for the standardized construction of ^"Integrated Outpatient Clinics for Cervical Cancer Prevention and Control^" in general hospitals at all levels. Methods This consensus systematically elaborates on the specific elements for establishing such integrated clinics and formulates the corresponding standards. Results It is anticipated that the consensus will promote the establishment of standardized, homogeneous, and high-efficiency frontline positions for cervical cancer prevention and control within general hospitals, thereby contributing to the strategic vision of accelerating the elimination of cervical cancer. Conclusion The formulation and promotion of the consensus aim to provide robust clinical practice support for accelerating the realization of China's strategic vision of eliminating cervical cancer.

Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.