1.Effect of Modified Duhuo Jisheng Mixture Regulating PI3K/Akt/mTOR Signaling Pathway on Synoviocyte Pyroptosis in Rabbit Models of Knee Osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Xuyi TAN ; Liang OU ; Gaoyan KUANG ; Min LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):170-179
ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture (JDJM) in treating synovial lesions in knee osteoarthritis (KOA). MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group (n=8) and a model group (n=35). The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage, with a modeling period of 6 weeks, resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group, celecoxib group, JDJM group and JDJM+740Y-P group, each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg-1, while the JDJM was administered a single dose of 6.8 mL·kg-1 (4.515 2 g·kg-1) of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway activator + JDJM group received 4.515 2 g·kg-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg-1 740Y-P. For a period of 6 weeks, the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period, the knee joint pain threshold and circumference were measured, and hematoxylin-eosin (HE) staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay (ELISA) measured the levels of interleukin-1β (IL-1β), interleukin-6 (IL-18) and tumor necrosis factor-α (TNF-α) in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, NOD-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and gasdermin D (GSDMD) in the synovial tissues. Immunohistochemical (IHC) assay was performed to assess the protein expression of NLRP3, Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD. ResultsCompared to the blank group, the model group showed a significant increase in knee joint circumference and decrease in pain threshold, the synovial tissue pathology score was higher (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid significantly increased (P<0.01). PI3K, Akt, mTOR phosphorylation as well as mRNA and protein expression increased (P<0.01), while the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD also significantly increased (P<0.01). Compared to the model group, the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold, the synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid decreased (P<0.01). The mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, NLRP3, Caspase-1 and GSDMD were reduced (P<0.01). Compared to the JDJM group, the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions, an increase in knee joint circumference, and a decrease in pain threshold. The synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid were higher (P<0.01). The mRNA and protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD increased (P<0.01). ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues, inhibiting pyroptosis, reducing inflammatory factor release, and protecting bony structures.
2.The role of H-type vessels as a mediator of subchondral bone remodeling and cartilage degeneration in the pathogenesis of knee osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Gaoyan KUANG ; Min LU
Journal of Chongqing Medical University 2025;50(9):1247-1252
There is a close relationship between subchondral bone remodeling and angiogenesis in knee osteoarthritis(KOA).Type H vessels,a newly identified subtype of bone vasculature,play a pivotal role in linking angiogenesis with osteogenesis by mediating signals through various cytokines,thereby regulating bone growth and homeostasis.During KOA development,mechanical loads and factors like transforming growth factor-β1(TGF-β1),platelet-derived growth factor-BB(PDGF-BB),vascular endothelial growth factor(VEGF)cause abnormal H-type vessel growth in subchondral bone and cartilage.This suggests that H-type vessel regulation might be a potential KOA treatment mechanism.This article explores the role of H-type vessels in subchondral bone remodeling and cartilage degeneration and the factors driving their abnormal growth,which provides a theoretical basis for further research and high-lights the potential of targeting H-type vessels for KOA treatment.
3.Exploring the factors affecting music-related quality of life in post-lingual deaf adults with cochlear implants
Ye YANG ; Xiaoyun QIAN ; Liguo GENG ; Yaofeng JIANG ; Junyan GAO ; Li HUANG ; Ao LI ; Ning ZHAO ; Yuqin XU ; Guangjie ZHU ; Xia GAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):27-33
Objective:To observe the feelings of listening to music and the importance of music in the daily life of post-lingual deaf adults with cochlear implants, and to explore the relevant influencing factors.Methods:This was a cross-sectional survey study. From January 2021 to August 2021,the Music-Related Quality of Life Scale was used to evaluate the music needs and music experiences of 63 post-lingual deaf adults who met the inclusion criteria, including 27 males and 36 females, aged (40.7±12.3) years, at the time of surgery (36.8±13.1) years, and with a preoperative hearing aid ineffective time of (3.9±5.8) years. Indicators analyzed included age, duration of ineffective preoperative hearing aid wear, preoperative music preference, duration of postoperative cochlear implant use, current hearing aid modality, and auditory rehabilitation outcomes. Whether the six factors mentioned above constituted an influence on the subjects′ music listening was investigated using SPSS 25.0 statistical software.Results:All of the observations in the scale were correlated with a single factor. The two sub-dimensions of music experience section were related to the effect of auditory rehabilitation. In the importance section, the effect of auditory rehabilitation was the influential factor of the dimension of "participation importance", and the preoperative enjoyment of music was the relevant influential factor of the dimension of "perceived importance". There was a significant difference between the groups when they were grouped by the above factors ( P value<0.05), while there was no statistically significance between the groups when they were grouped by other factors ( P value>0.05). Conclusions:Post-lingual deaf adults show the need and attempt to listen to music after cochlear implantation. The effectiveness of auditory rehabilitation and the degree of music preference preoperatively are two important factors that influence music listening in implant recipients. Once the level of auditory communication has been restored to a certain degree, it is important to pay more attention to the needs of music for implant recipients and train them in time, especially for those with music preferences preoperatively.
4.Pallidus Stimulation for Chorea-Acanthocytosis: A Systematic Review and Meta-Analysis of Individual Data
Weibin HE ; Chenhui LI ; Hongjuan DONG ; Lingmin SHAO ; Bo YIN ; Dianyou LI ; Liguo YE ; Ping HU ; Chencheng ZHANG ; Wei YI
Journal of Movement Disorders 2022;15(3):197-205
A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.
5.Mining prognostic marker of glioma based on weighted gene co-expression network analysis
Chunyu ZHANG ; Liguo YE ; Long WANG ; Yinqiu TAN ; Fanen YUAN ; Ye TAO ; Qianxue CHEN ; Daofeng TIAN
Journal of Chinese Physician 2021;23(4):529-533
Objective:To identify effective biomarkers for glioma patients.Methods:The mRNA expression profiles of 464 glioma patients with complete clinical follow-up information were downloaded from the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules related to World Health Organization (WHO) grading of glioma, and univariate and multivatiate Cox regression analysis were performed to identify gliomas survival-related genes.Results:In weighted gene co-expression analysis, the module Brown was significantly positively correlated with glioma WHO stage ( r=0.55, P<0.05). In univariate analysis, five genes (TAGLN2, IGFBP2, METTL7B, ARAP3, PLAT) that were most significantly associated with clinical prognosis were selected for multivariate survival analysis, and the prognosis model was established to calculate the risk score. The receiver operating characteristic curve (ROC) confirmed that the risk score had high accuracy in predicting the 1-, 3-, 5-year survival rate of glioma patients. The above survival analysis results were verified in the Cancer Genome Atlas (TCGA) database. Conclusions:We use mRNA expression profiles to establish prognostic markers for gliomas to assess the overall survival of patients with glioma.
6.The mass spectrometry analysis of serum biomarker 32 kD protein in first episode-schizophrenia
Ruixu HUAN ; Wan XING ; Yuan WENBIN ; Liang JINGWEN ; Luo YI ; Li KANG ; Liao CHANGZHENG ; Xu WENLI ; Ye CHANGBIN ; Zhu LEI ; Qi LIGUO
Chinese Journal of Nervous and Mental Diseases 2015;(8):482-486
Objective To analyze the constituent of the 32 kD protein band and its expression in schizophrenia se?rum. Methods Sixty schizophrenia patients and 58 health controls were recruited. The serum samples were collected and precipitated with 7%PEG. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to ob?tain the abnormal 32 kD proteins band in patients. This protein band was cut and then analyzed using mass spectrometric technique. Results The 32 kD protein band was present in 38 schizophrenia patients but not in control and positive rate was 63.33%. The mass spectrometric analysis showed that 32 kD protein band contained 14 proteins ranging from 30 kD to 35 kD, including 6 high-frequency proteins (cDNA coded protein 1 and 2, Apolin protein A-1, Isoform 2 of ficolin-2, Complement factor H and clusterin) and 8 low-frequency proteins (IgG H chain, zinc-alphg-2-glycoprotein, fermitin,family apolin protein L-1, isoform 10 of collectin-1, purine nucleoside, anne xin and cDNA coded protein 3). Three cD?NA coded unknown proteins were highly similar to complement C4-B, β2-glycoprotein and erythrocyte band 7 integral membrane protein. Conclusion There is a unknown specific 32 kD protein that is consisted mainly of fourteen proteins in serum of schizophrenia.
7.Intranasal administration of the conditioned medium of human umbilical cord-derived mesenchymal stem cells for treatment of cerebral ischemia-reperfusion injury
Liping SHEN ; Shuaishuai WANG ; Liguo DONG ; Xia SHEN ; Fang HUA ; Xinchun YE ; Guiyun CUI
Chinese Journal of Tissue Engineering Research 2013;(45):7891-7897
BACKGROUND:Cytokines and neurotrophic factors secreted from human umbilical cord blood-derived mesenchymal stem cells secrete have neuroprotective effects on cerebral ischemia-reperfusion injury, but there are few reports about intranasal administration of human umbilical cord blood-derived mesenchymal stem cellconditioned medium in the treatment of stroke.
OBJECTIVE:To investigate the protective effects of intranasal administration of human umbilical cord-derived mesenchymal stem cells-conditioned medium on neurologic function of rats with cerebral ischemia-reperfusion injury.
METHODS:Adult rats were subjected to 2 hours of right middle cerebral artery occlusion and the human umbilical cord-derived mesenchymal stem cells were isolated from the postpartum human cord. We made the conditioned medium of human umbilical cord-derived mesenchymal stem cells. Ischemic rats were randomized and assigned to three groups and were treated by intranasal routine starting 24 hours after middle cerebral artery occlusion with:(1) saline for control group;(2) Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 medium for medium control group;(3) conditioned medium treatment group (10mL/kg) daily for 14 days. Behavioral tests (foot fault test, and modified Neurological Severity Score) were performed before and at 1, 7, 14 days after middle cerebral artery occlusion.
RESULTS AND CONCLUSION:There was no difference in the behavioral tests among the three groups at postoperatively 1 day (P>0.05). Compared to the control and medium control group rats, respectively, rats in the conditioned medium group significantly improved functional outcome after stroke in days 7 and 14 (P<0.05). There was also no significant difference in functional tests between the control group and medium control group in days 7 and 14 (P>0.05). These results suggest that human umbilical cord-derived mesenchymal stem cells-conditioned medium via intranasal administration can significantly improve neurologic functional outcome after cerebral ischemia-reperfusion injury.

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