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.

Objective To explore the application value of different Trocar layouts in retroperitoneal laparoscopic partial nephrectomy for localized renal cell carcinoma, so as to provide reference for the layout of Trocar during operation. Methods The data of 137 patients with localized renal cell carcinoma who underwent retroperitoneal laparoscopic partial nephrectomy in our hospital during Sep. 2021 and Sep. 2024 were retrospectively collected, including 68 patients with umbrella layout(umbrella group)and 69 with trapezoidal layout(trapezoidal group). The operation-related indexes, renal function(glomerular filtration rate, serum creatinine), traumatic stress indexes including C-reactive protein(CRP), cortisol, and interleukin-6(IL-6), complications and recurrence rate were compared between the two groups. Results There were no significant differences in pathological results, negative rate of surgical margins, hospitalization time, complications, 1-year recurrence rate, 6-month glomerular filtration rate and serum creatinine between the two groups(P＞0.05). Compared with the trapezoidal group, the umbrella group had less intraoperative blood loss [(72.11±18.30)mL vs.(87.59±20.63)mL], shorter operation time [(88.15±16.92)min vs.(99.40±20.78)min], renal warm ischemia time [(14.68±4.60)vs.(19.27±6.11)min], bowel sound recovery time [(21.00±5.75)h vs.(25.78±4.89)h] and ambulation time [(1.72±0.48)d vs.(2.04±0.55)d](P＜0.05). The umbrella group had lower CRP [(10.02±2.78)mg/ L vs.(12.00±3.15)mg/ L] on the first day after surgery, lower CRP [(7.89±0.76)vs.(8.77±1.25)mg/L] on the third day after surgery, lower cortisol [(0.67±0.20)μmol/L vs.(0.89±0.28)μmol/L] on the first day after surgery, lower cortisol [(0.58±0.15)μmol/L vs.(0.69±0.12)μmol/L] on the third day after surgery, lower IL-6 [(28.20±6.74)ng/L vs.(35.16±7.30)ng/L] on the first day after surgery, and lower IL-6[(21.25±5.39)ng/L vs.(29.78±4.26)ng/L] on the third day after surgery(P＜0.05). Conclusion Compared with the trapezoidal Trocar layout, the umbrella Trocar layout for retroperitoneal laparoscopic partial nephrectomy in patients with localized renal cell carcinoma offers advantages such as minimal surgical trauma, shorter operation and renal warm ischemia time, and faster postoperative recovery.

Objective:Micro-and nanostructures with sharp disordered and rounded ordered features were fabricated on titanium surfaces,respectively,and their osteogenic potential was evaluated both in vitro and in vivo.Methods:Sharp disordered titanium surfaces(SLA-Ti)and rounded ordered titanium surfaces(Laser-Ti)were prepared using sandblast acid etching and high-repeti-tion-rate femtosecond laser,respectively.Smooth titanium(Ti)was used as the control group,SLA-Ti and Laser-Ti were used as the experimental groups.Characterization was conducted using scanning electron microscopy coupled with hydrophilicity assess-ments.The adhesion,elongation,and osteogenic differentiation capabilities of osteoblasts in vitro were evaluated through cell mor-phology observations,cytoskeletal fluorescence staining,cell viability assays,and PCR experiments.Osteogenic potential in vivo of rabbits was assessed through Micro CT scans and histological staining(HE and Masson).Results:The surface of Laser-Ti exhibits a rounded,ordered,multi-scale micro-and nano-morphology with the best hydrophilicity(P＜0.01).In vitro,it promotes cell adhe-sion,extension,and osteogenic differentiation,while in vivo,it enhances bone regeneration around the implants.Overall,a trend of Laser-Ti＞SLA-Ti＞Ti is observed,with a higher bone volume fraction(BV/TV)(P＜0.05),greater trabecular thickness(Tb.Th)(P＜0.05),an increased number of trabeculae(Tb.N)(P＜0.05),and a larger area of bone around the implants(P＜0.05).Conclusion:The rounded ordered micro-and nano-structures fabricated using high-repetition-rate fem-tosecond laser demonstrate enhanced osteoinductive capac-ity both in vitro and in vivo.

Objective:Micro-and nanostructures with sharp disordered and rounded ordered features were fabricated on titanium surfaces,respectively,and their osteogenic potential was evaluated both in vitro and in vivo.Methods:Sharp disordered titanium surfaces(SLA-Ti)and rounded ordered titanium surfaces(Laser-Ti)were prepared using sandblast acid etching and high-repeti-tion-rate femtosecond laser,respectively.Smooth titanium(Ti)was used as the control group,SLA-Ti and Laser-Ti were used as the experimental groups.Characterization was conducted using scanning electron microscopy coupled with hydrophilicity assess-ments.The adhesion,elongation,and osteogenic differentiation capabilities of osteoblasts in vitro were evaluated through cell mor-phology observations,cytoskeletal fluorescence staining,cell viability assays,and PCR experiments.Osteogenic potential in vivo of rabbits was assessed through Micro CT scans and histological staining(HE and Masson).Results:The surface of Laser-Ti exhibits a rounded,ordered,multi-scale micro-and nano-morphology with the best hydrophilicity(P＜0.01).In vitro,it promotes cell adhe-sion,extension,and osteogenic differentiation,while in vivo,it enhances bone regeneration around the implants.Overall,a trend of Laser-Ti＞SLA-Ti＞Ti is observed,with a higher bone volume fraction(BV/TV)(P＜0.05),greater trabecular thickness(Tb.Th)(P＜0.05),an increased number of trabeculae(Tb.N)(P＜0.05),and a larger area of bone around the implants(P＜0.05).Conclusion:The rounded ordered micro-and nano-structures fabricated using high-repetition-rate fem-tosecond laser demonstrate enhanced osteoinductive capac-ity both in vitro and in vivo.

Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.