1.Effects of Xiaozhong Zhitong Mixture (消肿止痛合剂) on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
Xiao HAN ; Tao LIU ; Yuan SONG ; Jie CHEN ; Jiaxuan SHEN ; Jing QIAO ; Hengjie WANG ; Lewen WU ; Yazhou ZHAO
Journal of Traditional Chinese Medicine 2025;66(16):1695-1703
ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture (消肿止痛合剂, XZM) in the treatment of diabetes foot ulcer (DFU). MethodsFifty SD rats were randomly divided into blank group, model group, XZM group, inhibitor group, XZM plus inhibitor group (combination group), with 10 rats in each group. Except for the blank group, rats were fed with high-sugar, high-fat, high-cholesterol diet, intraperitoneally injected with streptozotocin, and subjected to skin defect to establish DFU model. After successful modeling, the XZM group and the combination group were given 1 ml/(100 g·d)of XZM by gavage, while the blank group, model group, and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later, the inhibitor group and the combination group were intraperitoneally injected with 5 mg/(kg·d) of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration, the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin (HE) staining. The microvascular density (MVD) in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of Notch1 homolog (Notch1), Delta-like ligand 4 (Dll4), Delta-like ligand 4 (VEGF), and angiopoietin 2 (Ang-2), respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group, the epidermis exhibited excessive keratinization, vacuolar cytoplasm, and a large number of inflammatory cells infiltrating the tissue, while in the XZM group, a large amount of scab formation was observed in the epidermis, with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group, partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group, the MVD in the wound tissue increased in the model group, as well as the mRNA expression and protein levels of Notch1 and Dll4, while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased (P<0.05 or P<0.01). Compared to those in the model group, the MVD in the wound tissue of all medication groups significantly increased, and the mRNA and protein levels of Notch1 and Dll4 decreased, while VEGFA and Ang-2 mRNA expression and protein levels increased (P<0.05 or P<0.01). Compared to the XZM group, the inhibitor group and the combination group showed decreased MVD in wound tissue, increased Notch1 and Dll4 mRNA and protein levels, and decreased expression of VEGFA and Ang-2 mRNA and proteins (P<0.05 or P<0.01). ConclusionXZM can effectively promote wound healing in DFU rats, and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue, therey promoting angiogenesis.
2.Characteristics of Effective Pacing Strategies of 1 500-m Freestyle Medalists in World Swimming Championships
Xiaoqing LÜ ; Haoyuan WU ; Lewen HONG ; Ming LI ; Xuhong LI
Journal of Medical Biomechanics 2024;39(6):1168-1174
Objective To explore whether the medalists in 1 500-m freestyle swimming choose different pacing strategies from their competitors,so as to determine the most effective pacing strategy characteristics to obtain victory in swimming race.Methods The 1 500-m freestyle finalists in World Swimming Championships from 2003 to 2023 were selected as candidates of this study.According to the final ranking of the 175 elite athletes in the race,the split time,cumulative time were calculated,respectively.The differences of the main indicators in pacing strategies between medalists and their competitors were compared,and the above variables were selected for one-way ANOVA statistical analysis.Results The medalists had a significant speed advantage regardless of split time in the race,as well as the velocity of the starting stage,intermediate swim and end spurt(P<0.01).After the normalization of the cumulative time,the differences between the medalists and 4th-8th athletes in the percentage of split time and normalized velocity were mainly reflected in the last 400 m or so of the first and second half of the race(P<0.05).Regardless of whether they won medals or not,the pacing strategies of male freestyle swimmers were mostly reverse J-and U-shaped,while those of the female were mainly reverse J-shaped(90.9%).The diving start indicator(DSI)and end-spurt indicator(ESI)of medalists were higher,but the ESI of medalists was significantly different from that of 4th-8th athletes(P<0.05).Meanwhile,the coefficient of variation(CV)and the median and quartile of the density distribution of CV were significantly lower in intermediate stage.Conclusions All 1 500-m freestyle finalists follow a similar parabolic pacing strategies regardless of gender and final race ranking.Compared with their competitors,the medalists choose a relatively conservative starting strategy,a more even pace through the middle section of the race and a strong end-spurt.In summary,the reverse J-shape is an effective pacing strategy for the success of elite freestyle athletes in 1 500-m swimming competitions.
3.Characteristics of Effective Pacing Strategies of 1 500-m Freestyle Medalists in World Swimming Championships
Xiaoqing LÜ ; Haoyuan WU ; Lewen HONG ; Ming LI ; Xuhong LI
Journal of Medical Biomechanics 2024;39(6):1168-1174
Objective To explore whether the medalists in 1 500-m freestyle swimming choose different pacing strategies from their competitors,so as to determine the most effective pacing strategy characteristics to obtain victory in swimming race.Methods The 1 500-m freestyle finalists in World Swimming Championships from 2003 to 2023 were selected as candidates of this study.According to the final ranking of the 175 elite athletes in the race,the split time,cumulative time were calculated,respectively.The differences of the main indicators in pacing strategies between medalists and their competitors were compared,and the above variables were selected for one-way ANOVA statistical analysis.Results The medalists had a significant speed advantage regardless of split time in the race,as well as the velocity of the starting stage,intermediate swim and end spurt(P<0.01).After the normalization of the cumulative time,the differences between the medalists and 4th-8th athletes in the percentage of split time and normalized velocity were mainly reflected in the last 400 m or so of the first and second half of the race(P<0.05).Regardless of whether they won medals or not,the pacing strategies of male freestyle swimmers were mostly reverse J-and U-shaped,while those of the female were mainly reverse J-shaped(90.9%).The diving start indicator(DSI)and end-spurt indicator(ESI)of medalists were higher,but the ESI of medalists was significantly different from that of 4th-8th athletes(P<0.05).Meanwhile,the coefficient of variation(CV)and the median and quartile of the density distribution of CV were significantly lower in intermediate stage.Conclusions All 1 500-m freestyle finalists follow a similar parabolic pacing strategies regardless of gender and final race ranking.Compared with their competitors,the medalists choose a relatively conservative starting strategy,a more even pace through the middle section of the race and a strong end-spurt.In summary,the reverse J-shape is an effective pacing strategy for the success of elite freestyle athletes in 1 500-m swimming competitions.

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