1.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
2.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
3.Mechanism of Yantiao Prescription in Treating Lipopolysaccharide-induced Acute Lung Injury Based on Arachidonic Acid Metabolic Pathways
Pengcheng LI ; Tianyang CHEN ; Rong FANG ; Anna ZHANG ; Sijia WU ; Wei LIU ; Qian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):101-110
ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide (LPS)-induced acute lung injury (ALI), and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid (AA) in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight: normal group, model group, dexamethasone group (2 mg·kg-1), low-dose Yantiao prescription group (18 g·kg-1), and high-dose Yantiao prescription group (36 g·kg-1), with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days, and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to assess lung tissue pathology. The wet/dry weight ratio (W/D) and myeloperoxidase (MPO) activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry (LC-MS/MS). ResultsCompared with the conditions in the normal group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the model group was significantly increased (P<0.01). The alveolar structure in mice was severely damaged, with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased (P<0.01). The content of AA metabolites, including prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), 11(S)-hydroxy-eicosatetraenoic acid [11(S)-HETE], and 5-hydroxy-eicosatetraenoic acid (5-HETE) in serum and lung tissue was significantly increased (P<0.05), while the content of 11,12-epoxyeicosatrienoic acid (11,12-EET) and 14,15-epoxyeicosatrienoic acid (14,15-EET) in serum was significantly decreased (P<0.01). Compared with the results in the model group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the dexamethasone group, low-dose Yantiao prescription group, and high-dose Yantiao prescription group was significantly reduced (P<0.05). Mild thickening of alveolar walls, scattered inflammatory cell infiltration, and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced (P<0.01). The content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum from the dexamethasone group was significantly decreased (P<0.05), while the content of 14,15-EET in serum significantly increased (P<0.01), and the content of 5-HETE in lung tissue significantly decreased (P<0.01). In the low-dose and high-dose Yantiao prescription groups, the content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum and lung tissue was significantly decreased (P<0.05), while the content of 11,12-EET in both serum and lung tissue was significantly increased (P<0.05). ConclusionYantiao prescription has significant protective effects against LPS-induced ALI, which are related to its regulation of AA metabolic pathways in vivo.
4.Contamination risk and drug resistance analysis of Klebsiella pneumoniae in a medical institution in Minghang District, Shanghai, 2021‒2023
Sijia ZHANG ; Xing ZHANG ; Liang TIAN ; Yibin ZHOU ; Xiaosa WEN ; Jing WANG ; Zhiyin XU ; Min WU
Shanghai Journal of Preventive Medicine 2025;37(4):289-295
ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ2=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ2=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ2=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ2=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ2=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ2=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.
5.Danzhi Jiangtang Capsule improves renal vascular endothelial function in rats with diabetic nephropathy by downregulating the Notch1/NICD/MAML1 signaling pathway.
Sijia ZHU ; Jingcheng MA ; Yujiao ZHENG ; Chuanyun WU ; Jiangen ZHAO ; Lingxiu LI ; Li WANG ; Xuemei ZHOU
Journal of Southern Medical University 2025;45(10):2250-2257
OBJECTIVES:
To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN).
METHODS:
Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting.
RESULTS:
The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC.
CONCLUSIONS
DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
Animals
;
Male
;
Drugs, Chinese Herbal/therapeutic use*
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
Diabetic Nephropathies/drug therapy*
;
Receptor, Notch1/metabolism*
;
Kidney/blood supply*
;
Diabetes Mellitus, Experimental
;
Down-Regulation
;
Endothelium, Vascular/metabolism*
;
Nuclear Proteins/metabolism*
6.Genome sequences of H7N9 avian influenza virus in poultry-related environment in Henan Province in 2023
Bicong WU ; Xue LUO ; Shidong LU ; Yun SONG ; Baifan ZHANG ; Haiyan WEI ; Yifei NIE ; Hui XIA ; Sijia WAN ; Ying YE ; Xueyong HUANG ; Wanshen GUO ; Hongxia MA
Chinese Journal of Microbiology and Immunology 2024;44(5):377-381
Objective:To analyze the genetic evolution and molecular characteristics of H7N9 avian influenza virus (AIV) isolated in a live poultry market.Methods:Samples such as poultry feces, sewage, and hair removal machine and chopping board swabs were collected. Real-time fluorescent quantitative PCR was used to detect influenza A virus and H7N9 AIV in the samples. The whole genome of H7N9 AIV was amplified with influenza A virus universal primers and sequenced. BLAST and MEGA X were used for sequence alignment, phylogenetic analysis and molecular characterization.Results:Seven poultry-related environment samples were collected in the live poultry market in Xuchang city in February 2023, and four were positive for H7N9 AIV. The whole genome sequences of three H7N9 AIV isolates were successfully obtained, and the isolates shared high nucleotide identity in different genes (98.37%-100.00%). BLAST analysis showed they were highly identical to H7N9 strains isolated from domestic poultry in China from 2020 to 2021. Genetic evolution analysis showed that the three isolates clustered in the same branch and were closer to the recent environmental isolates than to the recent strains isolated from human or avian. Through comparison with the sequences of the representative strains in different periods, it was found that the isolated strains in this study showed high avian pathogenicity with four amino acids KRAA inserted at the cleavage site; the hemagglutinin receptor-binding site was QSG, which was an avian binding receptor; there was a G186I mutation in hemagglutinin. Mammalian-adaptive mutation E627K was not detected in polymerase basic protein 2. Mutations (R292K and I38T) associated with drug resistance to neuraminidase inhibitor (oseltamivir) and polymerase acidic protein inhibitor (baloshavir) were not detected, suggesting that these isolates remained susceptible to these drugs. A S31N mutation was found in M2 protein, indicating they were resistant to alkamines.Conclusions:The three H7N9 AIV strains isolated in the live poultry market have high avian pathogenicity, but there are no significant increase in mutations related to the binding ability to human receptors, mammalian pathogenicity, viral transmissibility, or drug resistance as compared with previous representative strains causing human or avian infection.
7.Qualitative study on early exercise rehabilitation experience and needs of elderly patients with total hip arthroplasty
Xiaoxia ZHU ; Man XU ; Sijia ZHAO ; Hong WU ; Huan ZHANG ; Liqin FU ; Jinxia JIANG ; Jing WU
Chinese Journal of Modern Nursing 2024;30(13):1745-1749
Objective:To understand the real experience and needs of early exercise rehabilitation in elderly patients with total hip arthroplasty (THA), so as to provide a preliminary basis for intervention research to meet the needs of patients.Methods:Using the purposive sampling method, a total of 12 elderly patients with THA from the First Affiliated Hospital of Naval Medical University from June to September 2021 were selected as the research objects for semi-structured in-depth interviews. Colaizzi 7-step method was used to analyze, summarize and extract the data.Results:The early exercise rehabilitation experience and needs of elderly THA patients could be summarized into four themes such as postoperative exercise being a difficult journey, the need for professional support, the need for external support and internally driven needs and 14 sub themes.Conclusions:There are various problems and needs for early exercise rehabilitation in elderly patients undergoing THA. It is necessary to strengthen communication among doctors, nurses and patients, understand their true feelings and provide personalized care and rehabilitation guidance to improve their treatment experience and enhance their satisfaction.
8.Construction and application of a pelvic floor muscle training program for patients with radical prostatectomy
Wenbo QIAO ; Sijia HOU ; Keping ZHU ; Yaqin LI ; Siyuan WU ; Ziyi QI ; Wei WANG
Chinese Journal of Nursing 2024;59(8):909-915
Objective To construct a pelvic floor muscle training program for patients undergoing radical prostatectomy,and to provide a reference for clinical practice.Methods The evidence related to pelvic floor muscle training in patients undergoing radical prostatectomy was systematically searched and the quality was evaluated.The draft of pelvic floor muscle training program for patients undergoing radical prostatectomy was constructed based on the KAP theory and it was demonstrated and revised by expert meetings.From February to March 2023,Delphi method was used to determine the final scheme.37 patients were selected as the control group and 38 patients as the experimental group to implement the scheme and evaluate the application effect.Results 2 rounds of Delphi consultations were conducted among 17 experts,and the recovery rate of the questionnaire was 100%.The expert authority coefficient was 0.89.The Kendall harmony coefficients of the importance and feasibility of the second round of consultation were 0.270 and 0.209(P<0.001).The coefficient of variation of importance and feasibility of items were 0~0.18 and 0~0.20.The final program included 3 first-level items,8 second-level items and 29 third-level items.1 month after surgery,there was no significant difference in urinary incontinence score(P=0.242)and there was significant difference in pelvic floor muscle training compliance(P=0.011)between 2 groups.Conclusion The program was applied preliminary in clinical practice and it was confirmed with scientific and practical meaning,so it can provide a reference for clinical nursing.
9.In vitro synergistic evaluation of Nisin and NaF on Streptococcus mutans
Jianying TENG ; Yushan SHI ; Sijia WU ; Sa WANG ; Yuan WANG ; Shuli DENG ; Huiming WANG
Journal of Practical Stomatology 2024;40(5):625-630
Objective:To study the effects of the combined application of NaF and Nisin on Streptococcus mutans(S.mutans).Meth-ods:The minimum inhibitory concentration(MIC)of Nisin and NaF against S.mutans was determined by microdilution method respec-tively.The fractional inhibitory concentration(FIC)was calculated by checkerboard method.The inhibition effect of the combination of NaF and Nisin at(NF)the same MIC concentration on acid production and acid resistance of S.mutans was detected.Crystal violet staining was used to detect the effects of NF in the inhibition of the biofilm formation,and the damage and dispersion of the established biofilms.The changes of the biofilms were observed by CLSM.Results:The MIC of NaF and Nisin was 0.6 mg/mL and 20 mg/mL re-spectively.The FIC was 0.75.The 1/8×MIC NF showed significantly higher inhibition on acid production and biofilm formation than 1/4×MIC NaF or Nisin(P<0.05),but it has no obvious dispersion effect on established biofilms.The 1/2×MIC NF showed stronger in-hibition effect on the acid resistance of S.mutans in the membrane than 1×MIC NaF or Nisin(P<0.05).At the concentration of 2x MIC,any component didn't cause obvious damage on the established biofilm structure.Conclusion:Nisin and NaF have synergistic in-hibitory effects on the proliferation,acid production,acid resistance and biofilm formation of S.mutans.
10.Changes of muscle activation during landing impact of human lower limbs during accumulation of running fa-tigue
Qian WU ; Mengli WEI ; Sijia CAO ; Tingting YU ; Yaping ZHONG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(10):1215-1223
Objective To investigate changes of muscle activation in the lower limbs during landing impact as running fatigue pro-gresses. Methods From November to December,2022,eleven male runners were recruited from Wuhan Sports University.They performed a steady-state run at 75%of their maximum heart rate and continued until Borg rating score≥17 or 90%of their maximum heart rate.Muscle activity data were collected using a Delsys wireless surface electromy-ography system,continuously recording the EMG of the quadriceps(vastus medialis,rectus femoris,vastus later-alis),hamstrings(biceps femoris,semitendinosus),gluteus maximus,lateral head of the gastrocnemius and tibia-lis anterior.The pre-activation,post-activation and co-activation characteristics of these lower limb muscles were analyzed. Results With fatigue accumulation during running,significant differences were observed in the pre-activation level of the tibialis anterior among different fatigue points(F=2.955,P=0.048),with the 100%fatigue point showing significantly higher pre-activation levels than the start(P=0.010);as well as post-activation levels of quadriceps(F=6.609,P=0.001),with higher levels at the 100%point compared to the start(P=0.011),33%(P=0.009)and 67%(P=0.043)fatigue points;co-activation ratios of ankle joint during the pre-activation phase(F=3.287,P=0.034),with a significantly higher co-activation ratio at the 100%fatigue point compared to the start(P=0.023). Conclusion As running fatigue accumulates,the central nervous system adjusts the activation levels of various lower limb muscles to modify impact posture,reducing the risk of injury from accumulated lower limb loads.

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