Objective To investigate the dynamic features of patients with patellofemoral pain(PFP)during running by using support vector machine(SVM)classifier and feature selection method,so as to provide a theoretical support for the prevention and rehabilitation of PFP.Methods An SVM classification model was used to classify healthy individuals(n=13),PFP patients with long-term disease course(n=13),and PFP patients with short-term disease course(n=10)based on their dynamic features during running.The most effective minimum feature set was selected through feature selection method.Results The accuracy rate of the constructed classification model was 83.3%.The minimum feature set selected contained 3 key features.PFP patients with short-term disease course showed a delay in the appearance of impact valleys and active peaks,while PFP patients with long-term disease course showed a lower impact peak-valley slope.Conclusions PFP patients with short-term disease course mainly showed a prolonged shock absorption process and a delayed propulsion action,while PFP patients with long-term disease course showed the most significant feature of having a lower vertical reaction force impact peak-valley slope.These features revealed the specific characteristics of PFP at different stages of the disease,providing a basis for developing individualized rehabilitation programs.

Objective By applying the long short-term memory(LSTM)neural network model and using lower body landmark coordinates obtained from a markerless motion capture system as inputs,to estimate ground reaction force(GRF)curves during running.Methods The video images and GRF data of 59 amateur runners during running were collected by the markerless motion capture system and three-dimensional(3D)force plates.The LSTM model was established,and the 3D coordinates of 11 lower body landmarks,obtained via the Theia3D markerless system,were used as inputs to estimate the 3D GRF curves during the stance of running.The estimation performance was evaluated using correlation coefficients r,root mean square error(RMSE),and normalized root mean square error(nRMSE)by comparing LSTM model estimation and force plate measurement.Statistical parametric mapping was used to analyze differences in GRF curves estimated by the LSTM model and measured by the force plate,while paired t-tests were used to assess differences in GRF characteristics between model estimation and actual measurement.Results A strong correlation(r＞0.85,P＜0.001)and lower error(RMSE＜0.3 body weight,nRMSE＜15％)was found between the LSTM model estimation and actual measurements.No significant difference was found in GRF curve intervals between LSTM model estimation and actual measurements.There was no significant difference in GRF characteristics between LSTM model estimation and actual measurements(P＞0.05).Conclusions Based on the LSTM model,the 3D GRF curves can be effectively estimated by lower body landmark coordinates obtained from the makerless motion capture system,thereby acquiring the highly accurate GRF characteristics.The LSTM model developed in this study can be used to monitor injury risks during running in outdoor environments.

Objective By applying the long short-term memory(LSTM)neural network model and using lower body landmark coordinates obtained from a markerless motion capture system as inputs,to estimate ground reaction force(GRF)curves during running.Methods The video images and GRF data of 59 amateur runners during running were collected by the markerless motion capture system and three-dimensional(3D)force plates.The LSTM model was established,and the 3D coordinates of 11 lower body landmarks,obtained via the Theia3D markerless system,were used as inputs to estimate the 3D GRF curves during the stance of running.The estimation performance was evaluated using correlation coefficients r,root mean square error(RMSE),and normalized root mean square error(nRMSE)by comparing LSTM model estimation and force plate measurement.Statistical parametric mapping was used to analyze differences in GRF curves estimated by the LSTM model and measured by the force plate,while paired t-tests were used to assess differences in GRF characteristics between model estimation and actual measurement.Results A strong correlation(r＞0.85,P＜0.001)and lower error(RMSE＜0.3 body weight,nRMSE＜15％)was found between the LSTM model estimation and actual measurements.No significant difference was found in GRF curve intervals between LSTM model estimation and actual measurements.There was no significant difference in GRF characteristics between LSTM model estimation and actual measurements(P＞0.05).Conclusions Based on the LSTM model,the 3D GRF curves can be effectively estimated by lower body landmark coordinates obtained from the makerless motion capture system,thereby acquiring the highly accurate GRF characteristics.The LSTM model developed in this study can be used to monitor injury risks during running in outdoor environments.

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

Objective To investigate the dynamic features of patients with patellofemoral pain(PFP)during running by using support vector machine(SVM)classifier and feature selection method,so as to provide a theoretical support for the prevention and rehabilitation of PFP.Methods An SVM classification model was used to classify healthy individuals(n=13),PFP patients with long-term disease course(n=13),and PFP patients with short-term disease course(n=10)based on their dynamic features during running.The most effective minimum feature set was selected through feature selection method.Results The accuracy rate of the constructed classification model was 83.3%.The minimum feature set selected contained 3 key features.PFP patients with short-term disease course showed a delay in the appearance of impact valleys and active peaks,while PFP patients with long-term disease course showed a lower impact peak-valley slope.Conclusions PFP patients with short-term disease course mainly showed a prolonged shock absorption process and a delayed propulsion action,while PFP patients with long-term disease course showed the most significant feature of having a lower vertical reaction force impact peak-valley slope.These features revealed the specific characteristics of PFP at different stages of the disease,providing a basis for developing individualized rehabilitation programs.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P＜0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P＜0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P＜0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0～80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P＜0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.

Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0～40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P＜0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P＜0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P＜0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.