BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Objective To investigate the anti-inflammatory properties of bergaptenand its inhibition of bone resorption in the treatment of periodontitis,as well as its potential underlying mechanisms.Methods A total of 35 male Wistar rats were randomly di-vided into five groups(control group,model group,and low-,medium-,and high-dose bergapten groups,with 7 rats in each group).Except for the control group,periodontitis was induced in all other groups by orthodontic ligation of the bilateral maxillary first molars(M1)and feeding a high-sugar diet.After successful modeling,the control and model groups received gavage of isotonic saline,while the bergapten groups received gavage of 50,100,and 200 mg/kg bergapten,respectively,once daily for 4 consecutive weeks.Perio-dontal symptoms were observed,and GI,SBI grades,and PLI scores were recorded.Rats were sacrificed within 24 hours after the last administration,and their maxillae were immediately subjected to Micro-CT scanning to assess alveolar bone resorption.Histopathological changes in the periodontal tissues were observed using HE staining,and serum levels of pro-inflammatory cytokines(IL-6 and IL-1β)were measured by ELISA.Results Compared with the control group,the model group exhibited significantly higher levels of IL-6,IL-1β,GI,SBI grades,PLI scores,and CEJ-ABC distance,while bone volume to total volume ratio(BV/TV),trabec-ular number(Tb.N),and trabecular thickness(Tb.Th)were significantly reduced(P＜0.001).In comparison to the model group,the bergapten groups(with the exception of the low-dose group for IL-6)demonstrated reductions in IL-6,IL-1β levels,GI,SBI grades,PLI scores,and CEJ-ABC distance,with the medium-dose group showing the most pronounced effect(except for IL-6).Conclusion Bergapten can effectively prevent and treat periodontitis by inhibiting the secretion of IL-6 and IL-1β cytokines,achieving anti-inflam-matory effects and inhibiting bone resorption.

Objective The study aimedto investigate the effects and metabolic mechanisms of Gegen Qinlian Decoction(GQD)containing serum on hypoxia-induced glucose metabolism in L02 cells.Methods The effects of five hypoxia durations(6,12,18,24,and 48 hours)on glucose consumption and cell viability of L02 cells were examined under hypoxic conditions to determine the optimal hypoxia time.Normal hepatocytes served as the normal control group.L02 cells with hypoxia-induced reduction in glucose consumption were divided into several groups:hypoxia group,metformin 2 mmol/L group,and 25 g/kg GQD groups treated with 5%,10%,and 15%GQD contain-ing serum.Glucose consumption was used as an indicator of drug efficacy.High-resolution liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)was employed to collect metabolite signals from each group.Data were analyzed by using Progenesis QI software,and potential biomarkers were identified through online databases such as HMDB.Finally,metabolic pathways of potential biomarkers were analyzed via the Metabo Analyst 5.0 website.Results An 18 hour hypoxia period was identified as the optimal duration for the replication of the hypoxia-induced L02 cell model.GQD containing serums at 5%and 10%significantly increased glucose consumption in hypoxia-induced L02 cells after 18 hours.14 biomarkers of hypoxia-induced L02 cells were identified,with the levels of 13 biomarkers significantly increased and 1 biomarker significantly decreased.GQD containing serum notably regulated the levels of 3 biomarkers.Conclusion GQD containing serum might improve hypoxia-induced abnormal glucose metabolism in L02 cells and enhance glucose consumption by modulating glycero-phospholipid metabolism,glycosylphosphatidylinositol biosynthesis,and sphingolipid metabolism.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective:To study the effect and mechanism of ganoderma lucidum polysaccharide peptide(GLPP)on renal anti oxidative stress and immune inflammation in diabetes nephropathy mice.Methods:The C57 male mice model of diabetes nephropathy was established by streptozotocin combined with high glucose and high-fat diet.Sixty diabetes nephropathy mice were divided into model group,losartan group,GLPP group(low,medium and high dose groups),GLPP high-dose+losartan group,with 10 mice in each group,10 mice fed with normal diet as the blank group.The losartan group was given 10 mg/kg losartan by gavage,and GLPP low,medium and high dose groups was given 50,100,and 200 mg/kg GLPP by gavage,while the GLPP high-dose+losartan group were given 200 mg/kg GLPP+10 mg/kg losartan by gavage.The blank group and model group were given physiological saline by gavage.After gastric lavage,observe the diet,water intake,renal pathology,structure,and apoptosis of renal tubular epithelial cells in mice,and analyze the levels of blood biochemical indicators,immune inflammation,oxidative stress indicators,and expression of apoptosis/cycle regulatory proteins in mice.Results:Compared with the blank group,the model group showed an increase in blood biochemical indicators such as Scr,BUN,TC,TG and GSP(P<0.05),as well as inflammation indicators such as level of IL-6 and TNF-α、MCP-1 were decreased(P<0.05),the oxidative stress indicator MDA was increased,T-AOC,GSH-PX,SOD were decreased(P<0.05),the apoptosis rate of renal tubular epithelial cells were increased(P<0.05),the expression levels of Bax,Caspase-3,P53,P21 were all increased,and the expression levels of Bcl-2 and Cyclin D1 were decreased(P<0.05).Compared with the model group,the losartan group,GLPP dose groups,GLPP high-dose+losartan group Scr,BUN,TC,TG,GSP,IL-6,TNF-α,MCP-1,MDA levels,apoptosis rate of renal tubular epithelial cells,Bax,Caspase-3,P53,P21 expression levels were all reduced,while T-AOC,SOD,GSH-PX levels,Bcl-2,and Cyclin D1 expression levels were all increased.Renal pathological changes were improved,and mitochondrial swelling was reduced.The GLPP high-dose+losartan group showed the most significant improvement(P<0.05).Conclusion:GLPP can reverse the renal injury in diabetes nephropathy mice,which may be related to the inhibition of apoptosis of renal tubular epithelial cells by alleviating renal oxidative stress and immune inflammatory damage.