1.Risk factors of malaria infection and risk prediction model research in in labor export in Langfang City
Xuejun ZHANG ; Kun ZHAO ; Jing ZHAO ; ZHUO WANG ; Qiang GUO ; Jie XIAO ; Juanjuan GUO ; Jinhong PENG
Journal of Public Health and Preventive Medicine 2025;36(1):118-122
Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school (OR=1.723,95% CI:1.361-2.173), and residence in rural areas(OR=2.091,95%CI:1.760 -3.100)were risk factors (OR>1), while protective measures(OR=0.826,95% CI : 0.781 - 0.901) and high malaria education scores (OR=0.872,95% CI : 0.621 - 0.899)were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.
2.Research and Application of Scalp Surface Laplacian Technique
Rui-Xin LUO ; Si-Ying GUO ; Xin-Yi LI ; Yu-He ZHAO ; Chun-Hou ZHENG ; Min-Peng XU ; Dong MING
Progress in Biochemistry and Biophysics 2025;52(2):425-438
Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.
3.Analysis of gemcitabine adverse drug reactions and risk factors in Inner Mongolia
Shengnan YANG ; Wei SHI ; Yufang ZHAO ; Zhien LIU ; Wenpu LEI ; Yanan ZHANG ; Ke ZHAO ; Hao GUO
China Pharmacy 2025;36(4):486-490
OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions (ADR) of gemcitabine for injection in national centralized volume-based procurement (hereinafter referred to as “centralized procurement”), and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023; basic information of patients, drug use status, patient outcomes, rational drug use and other information were collected, and the occurrence characteristics of ADRs with leukopenia, myelosuppression, neutropenia, thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender, age, combination of antitumor drugs, original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports (315 patients) of gemcitabine-induced ADR were included in this study, with a male-to-female ratio of 1.42∶1 and age of (61.17±9.13) years. The primary malignant tumor was pancreatic cancer (73 cases, 23.17%). Leukopenia, myelosuppression and nausea were the most common ADR, followed by neutropenia, thrombocytopenia, liver dysfunction and so on. The severity grade of ADR was mainly 1-2, and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia (RR=2.154, 95%CI: 1.218- 3.807, P=0.008; RR=3.099, 95%CI: 1.240-7.744, P=0.016); gender (female) was a risk factor for leukopenia and liver dysfunction (RR=0.508, 95%CI: 0.302-0.853, P=0.010; RR=0.301, 95%CI: 0.102-0.887, P=0.029). In terms of drug use rationality, there were 143 cases (45.40%) of drug 126.com use in accordance with the indications of the label, and 172 cases (54.60%) of off-label drug use. Among them, the primary malignant tumors were bladder cancer, bile duct cancer and ovarian cancer, which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels, and most ADRs have good outcomes. Gender (female) and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition, and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.
4.Follow-up study of left heart valve regurgitation after implantation of left ventricular assist device
Junjiang LIU ; Wenrui MA ; Dingqian LIU ; Yun ZHAO ; Lili DONG ; Zhe LUO ; Kefang GUO ; Chunsheng WANG ; Xiaoning SUN
Chinese Journal of Clinical Medicine 2025;32(1):72-77
Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P=0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.
5.Spectrum-effect Relationship of Bupleuri Radix Processed with Trionyx sinensis Blood for Yin Deficiency Based on Saponins
Mengyu HOU ; Xia ZHAO ; Zhiyu GUO ; Ting LIU ; Yuexing MA ; Yaohui YE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):147-155
ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood, and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM (version 2012). A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine (T3), thyroxine (T4), cyclic adenosine phosphate (cAMP), and cyclic guanosine phosphate (cGMP). The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database (TCMSP), The Encyclopedia of Traditional Chinese Medicine (ETCM), and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). Furthermore, the Online Mendelian Inheritance in Man (OMIM), GeneCards, TTD, DisGeNET, and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group, the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP, cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B1 > saikosaponin B2 > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A, D, B1, and B2 had higher VIP values. Network pharmacology predicted a total of 30 common targets, which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9, kinase insert domain receptor (KDR), and mammalian target of rapamycin (mTOR) and higher mRNA level of mouse double minute 2 homolog (MDM2) than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome, which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.
6.Modified Xiehuangsan Regulates Microglial Polarization and TLR4/MyD88/NF-κB Pathway to Treat Tic Disorders in Rats
Mengjie ZHAO ; Qiong ZHAO ; Cuiling YANG ; Hongyun ZHOU ; Xiangjuan SUN ; Xinyi GUO ; Sajiyue HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):10-18
ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders (TD) based on microglial polarization and the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor (NF)-κB pathway. MethodsSeventy-two Sprague-Dawley (SD) rats were randomly assigned into six groups: control, model, tiapride (0.025 g·kg-1), and low-, medium-, and high-dose (12, 24, 48 g·kg-1, respectively) modified Xiehuangsan, with 12 rats in each group. Except the control group, the other groups received intraperitoneal injection of 3,3'-iminodipropionitrile (IDPN) for 7 consecutive days for the modeling of TD. After successful modeling, the control and model groups were given normal saline via gavage, and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention, rat behaviors were observed, and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-4, TLR4, MyD88, and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 (Iba1), Fc receptor family for immunoglobulin (Ig)G type Ⅲ (CD16), mannose receptor (CD206), TLR4, MyD88, and NF-κB p65 in the striatum. ResultsCompared with the control group, the model group showed increased stereotyped behaviors, locomotor activity, total movement distance, and movement speed, shortened resting time (P<0.01), and noticeable pathological changes in the striatum. Compared with the model group, the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior, locomotor activity, total movement distance, and movement speed, prolonged resting time (P<0.05, P<0.01), and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups, the high-dose group had the best intervention effect and the mildest pathological changes. Therefore, the high-dose group was selected for further research. Compared with the control group, the modeling of TD increased Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the mRNA levels of IL-1β and TNF-α (P<0.05, P<0.01), down-regulated the mRNA level of IL-4 (P<0.05), up-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.05, P<0.01), and up-regulated the protein level of NF-κB p65 (P<0.01). Compared with the model group, modified Xiehuangsan reduced Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the protein level of CD206 (P<0.05, P<0.01), down-regulated the mRNA levels of IL-1β and TNF-α (P<0.05), up-regulated the mRNA level of IL-4 (P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, and NF-κB p65 (P<0.05, P<0.01). ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.
7.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
8.Characteristic Analysis of Effective Components and Compounds of TCM for Prevention and Treatment of Breast Cancer Based on Wnt/β-catenin Signaling Pathway Targeting
Haoyang WANG ; Lin GUO ; Hui ZHAO ; Lihua CAO ; Na LI ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):282-290
Breast cancer is a kind of malignant tumor with a complex mechanism, and its morbidity and mortality are increasing year by year, which seriously threatens women's health. At present, the main clinical treatments are surgical resection, radiotherapy, chemotherapy, and drug therapy, but they are often accompanied by side effects and adverse reactions, which affect the therapeutic effect. Traditional Chinese medicine (TCM) has the advantages of multi-component and multi-target treatment in the fight against breast cancer. The wnt/β-catenin signaling pathway is one of the classic pathways in cancer research. Abnormally activated Wnt/β-catenin signaling pathway inhibits β-catenin degradation by blocking the formation of Axin/glycogen synthase kinase 3β/adenomatous polyposis coli complex, thus promoting β-catenin nuclear metastasis, and it binds to T cell transcription factor/lymphoenhancer factor-1 to initiate downstream target genes and further interfere with the proliferation, migration, and invasion of tumor cells to affect the tumor process. Previous studies have shown that TCM monomers and compounds can mediate the Wnt/β-catenin signaling pathway to inhibit the malignant phenotype of breast cancer cells, thus playing an anti-breast cancer role, and the biochemical process involved in the regulation of therapeutic drugs has not been systematically combed. By analyzing and collating Chinese and foreign literature at the present stage, this paper discussed the association mechanism between Wnt/β-catenin signaling pathway and breast cancer and analyzed the internal mechanism of TCM monomers and compounds in mediating Wnt/β-catenin signaling pathway to exert anti-breast cancer effect. The statistical results showed that the flavonoids, alkaloids, and terpenoids in TCM monomers could target the Wnt/β-catenin signaling pathway and block the further development of malignant phenotype of breast cancer cells. TCM compounds with functions of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and tonifying kidney and liver were commonly used to intervene in the Wnt/β-catenin signaling pathway to prevent breast cancer. Compared with the current inhibitors of Wnt/β-catenin signaling pathway, the application of TCM monomers and compounds is expected to bring low-toxicity and high-efficiency breast cancer treatment drugs to the clinical practice, and the existing results provide a reference for the subsequent screening, research, and development of TCM small-molecule compounds and TCM compounds against breast cancer.
9.Metformin exerts a protective effect on articular cartilage in osteoarthritis rats by inhibiting the PI3K/AKT/mTOR pathway
Tianjie XU ; Jiaxin FAN ; Xiaoling GUO ; Xiang JIA ; Xingwang ZHAO ; Kainan LIU ; Qian WANG
Chinese Journal of Tissue Engineering Research 2025;29(5):1003-1012
BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.
10.Effect of transcranial magneto-acousto-electrical stimulation on the plasticity of the prefrontal cortex network in mice
Shuai ZHANG ; Zichun LI ; Yihao XU ; Xiaofeng XIE ; Zhongsheng GUO ; Qingyang ZHAO
Chinese Journal of Tissue Engineering Research 2025;29(6):1108-1117
BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P<0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P>0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.


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