This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

OBJECTIVES: To study the effects of early respiratory training combined with swallowing function training on physical development and neurodevelopment at a corrected gestational age of 6 months in infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 69 BPD infants who could not be fed completely orally were prospectively selected from the Department of Neonatology of Hunan Children's Hospital between January 2018 and January 2021. Based on a random number table, the infants were divided into a conventional group (35 cases) and a training group (34 cases) (with 8 cases lost to follow-up; the final follow-up included 31 cases in the training group and 30 cases in the conventional group). Both groups received routine clinical treatment and care, while the training group additionally received respiratory and swallowing function training until the infants could independently feed orally. The weight, length, Gesell Developmental Schedule (GDS) results, readmission rate, and multiple readmission rate (two or more admissions) were compared between the two groups at a corrected age of 6 months. RESULTS: At corrected gestational age of 6 months, the training group had higher weight, length, and GDS scores in personal-social, language, gross motor, fine motor, and adaptive development compared to the conventional group (P<0.05). The readmission rate and multiple readmission rate were lower in the training group compared to the conventional group (P<0.05). CONCLUSIONS Early respiratory training combined with swallowing function training for BPD infants in a neonatal intensive care unit setting helps improve physical and neurological development and reduces the readmission rate.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; Prospective Studies ; Male ; Female ; Infant ; Deglutition/physiology* ; Gestational Age ; Infant, Newborn ; Breathing Exercises ; Child Development

Objective:To investigate the biomechanical correlation between ankle instability and osteochondral lesions of the talus (OLT) under loading conditionsMethods:A healthy 29-year-old male volunteer was selected for the study. A 64-slice spiral CT scan of the right lower limb was performed to construct a detailed finite element model of the ankle joint, including ligaments and cartilage. Three injury models were created: models of distal tibiofibular syndesmosis injury, lateral collateral ligament injury, and a combined injury of the distal tibiofibular syndesmosis and lateral collateral ligament. Differences in stress distribution on the tibiotalar joint surface, talus stress, and talus displacement were analyzed through anterior drawer test, inversion stress test, and external rotation stress test.Results:In the anterior drawer test, as the forward traction force increased (40, 60, 80, 100, 120, 140, and 150 N), all the injury models showed a progressive increase in tibiotalar joint surface stress, talus stress, and talus displacement. The combined injury model showed the highest tibiotalar joint surface stress (32.6 MPa), while the lateral collateral ligament injury model demonstrated the highest talus stress (56.5 MPa). Talus displacement increased significantly with traction, reaching the maximum (4.88 mm) in the combined injury model under 150 N. In the inversion stress test, stress on the tibiotalar joint surface in the lateral collateral ligament injury model was concentrated on the posterior-lateral and posterior-medial regions, whereas in the combined injury model, stress on the tibiotalar joint surface was predominantly concentrated in the posterior-medial region. Talus stress was localized to the talus neck and body in all the models, with the combined injury model showing the largest talus displacement (8.46 mm). In the external rotation stress test, stress on the tibiotalar joint surface was mainly distributed in the posterior-medial, posterior-lateral, and anterior-lateral regions in all the models. Talus stress was concentrated at the talus neck and body. The combined injury model exhibited the greatest talus displacement (12.50 mm).Conclusion:Ankle instability, particularly from combined injuries of the distal tibiofibular syndesmosis and lateral collateral ligament, significantly increases the stress concentration and talus displacement under loading conditions, thus elevating the risk of OLT.

Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

BACKGROUND:As a new treatment method,local injection of medical ozone has anti-inflammatory,analgesic and immunomodulatory effects on injured skeletal muscle tissue,but its mechanism of action is still lacking systematic research.OBJECTIVE:To observe the intervention effect of medical ozone on skeletal muscle crush injury of rabbit models,and to analyze the differential gene expression of injured rabbit tibialis anterior muscle after ozone treatment through RNA-sequencing and tandem mass tag labeled quantitative proteomic technology,in order to partially reveal the molecular mechanism of medical ozone treatment for skeletal muscle injury.METHODS:Eighteen Japanese white rabbits were randomly divided into a blank group,a model group,and an ozone group,with 6 rabbits in each group.Rabbit tibialis anterior muscle compression injury models were established in the latter two groups.After 12 hours of model establishment,2 mL of medical ozone with a mass concentration of 30 μg/mL was injected into the injured muscle of rabbits in the ozone group.Tissue samples were taken 3 days after ozone treatment.Hematoxylin-eosin staining was used to observe the morphological changes of skeletal muscle.RNA sequencing and tandem mass spectrometry tag were used to detect rabbit tibialis anterior muscle tissue.Bioinformatics analysis was used to explore the biological processes of differentially expressed genes and proteins between groups and then to investigate the molecular mechanism of ozone treatment of skeletal muscle injury.RESULTS AND CONCLUSION:After 3 days of ozone treatment,compared with the blank group,the model group showed swelling of cells,infiltration of inflammatory cells,and partial dissolution of muscle fibers.Compared with the model group,cell edema was alleviated and the number of inflammatory cells was reduced in the ozone group.(2)The results of RNA sequencing and bioinformatics analysis showed that compared with the blank group,596 differentially expressed genes were screened in the model group.Compared with the model group,405 differentially expressed genes were screened in the ozone group.There were a total of 194 differentially expressed genes shared among these differentially expressed genes.Proteomic analysis results exhibited that compared with the blank group,the model group contained 138 differentially expressed proteins.Compared with the model group,242 differentially expressed proteins were determined in the ozone group.There were 66 differentially expressed proteins shared between the two comparison groups.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on differentially expressed genes/proteins,and it was found that they were mainly enriched in the PI3K-Akt signaling pathway,Ras signaling pathway,and MAPK signaling pathway.It is indicated that medical ozone may promote the repair of injured muscle through regulating PI3K/Akt/NF-κB and Ras/MAPK/NF-κB signaling pathway by acting on target genes,such as Syk,FGF16,CSF-1,and MRAS.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.

BACKGROUND:As a new treatment method,local injection of medical ozone has anti-inflammatory,analgesic and immunomodulatory effects on injured skeletal muscle tissue,but its mechanism of action is still lacking systematic research.OBJECTIVE:To observe the intervention effect of medical ozone on skeletal muscle crush injury of rabbit models,and to analyze the differential gene expression of injured rabbit tibialis anterior muscle after ozone treatment through RNA-sequencing and tandem mass tag labeled quantitative proteomic technology,in order to partially reveal the molecular mechanism of medical ozone treatment for skeletal muscle injury.METHODS:Eighteen Japanese white rabbits were randomly divided into a blank group,a model group,and an ozone group,with 6 rabbits in each group.Rabbit tibialis anterior muscle compression injury models were established in the latter two groups.After 12 hours of model establishment,2 mL of medical ozone with a mass concentration of 30 μg/mL was injected into the injured muscle of rabbits in the ozone group.Tissue samples were taken 3 days after ozone treatment.Hematoxylin-eosin staining was used to observe the morphological changes of skeletal muscle.RNA sequencing and tandem mass spectrometry tag were used to detect rabbit tibialis anterior muscle tissue.Bioinformatics analysis was used to explore the biological processes of differentially expressed genes and proteins between groups and then to investigate the molecular mechanism of ozone treatment of skeletal muscle injury.RESULTS AND CONCLUSION:After 3 days of ozone treatment,compared with the blank group,the model group showed swelling of cells,infiltration of inflammatory cells,and partial dissolution of muscle fibers.Compared with the model group,cell edema was alleviated and the number of inflammatory cells was reduced in the ozone group.(2)The results of RNA sequencing and bioinformatics analysis showed that compared with the blank group,596 differentially expressed genes were screened in the model group.Compared with the model group,405 differentially expressed genes were screened in the ozone group.There were a total of 194 differentially expressed genes shared among these differentially expressed genes.Proteomic analysis results exhibited that compared with the blank group,the model group contained 138 differentially expressed proteins.Compared with the model group,242 differentially expressed proteins were determined in the ozone group.There were 66 differentially expressed proteins shared between the two comparison groups.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on differentially expressed genes/proteins,and it was found that they were mainly enriched in the PI3K-Akt signaling pathway,Ras signaling pathway,and MAPK signaling pathway.It is indicated that medical ozone may promote the repair of injured muscle through regulating PI3K/Akt/NF-κB and Ras/MAPK/NF-κB signaling pathway by acting on target genes,such as Syk,FGF16,CSF-1,and MRAS.

Objective:To investigate the biomechanical correlation between ankle instability and osteochondral lesions of the talus (OLT) under loading conditionsMethods:A healthy 29-year-old male volunteer was selected for the study. A 64-slice spiral CT scan of the right lower limb was performed to construct a detailed finite element model of the ankle joint, including ligaments and cartilage. Three injury models were created: models of distal tibiofibular syndesmosis injury, lateral collateral ligament injury, and a combined injury of the distal tibiofibular syndesmosis and lateral collateral ligament. Differences in stress distribution on the tibiotalar joint surface, talus stress, and talus displacement were analyzed through anterior drawer test, inversion stress test, and external rotation stress test.Results:In the anterior drawer test, as the forward traction force increased (40, 60, 80, 100, 120, 140, and 150 N), all the injury models showed a progressive increase in tibiotalar joint surface stress, talus stress, and talus displacement. The combined injury model showed the highest tibiotalar joint surface stress (32.6 MPa), while the lateral collateral ligament injury model demonstrated the highest talus stress (56.5 MPa). Talus displacement increased significantly with traction, reaching the maximum (4.88 mm) in the combined injury model under 150 N. In the inversion stress test, stress on the tibiotalar joint surface in the lateral collateral ligament injury model was concentrated on the posterior-lateral and posterior-medial regions, whereas in the combined injury model, stress on the tibiotalar joint surface was predominantly concentrated in the posterior-medial region. Talus stress was localized to the talus neck and body in all the models, with the combined injury model showing the largest talus displacement (8.46 mm). In the external rotation stress test, stress on the tibiotalar joint surface was mainly distributed in the posterior-medial, posterior-lateral, and anterior-lateral regions in all the models. Talus stress was concentrated at the talus neck and body. The combined injury model exhibited the greatest talus displacement (12.50 mm).Conclusion:Ankle instability, particularly from combined injuries of the distal tibiofibular syndesmosis and lateral collateral ligament, significantly increases the stress concentration and talus displacement under loading conditions, thus elevating the risk of OLT.