1.Repetitive trans-spinal magnetic stimulation promotes motor function recovery in mice after spinal cord injury
Haiwang SONG ; Guanhua JIANG ; Yingying MU ; Shanyu FU ; Baofei SUN ; Yumei LI ; Zijiang YU ; Dan YANG
Chinese Journal of Tissue Engineering Research 2025;29(11):2252-2260
BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.
2.Hei Xiaoyaosan Modulates Oxidative Stress and Apoptosis to Exert Neuroprotective Effect in Alzheimer's Disease Rats
Yiqin CHEN ; Jiao YANG ; Wenli PEI ; Yumei HAN ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):99-107
ObjectiveTo explore the role and mechanism of Hei Xiaoyaosan in regulating the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in cascade modulation of oxidative stress and apoptosis for preventing and treating Alzheimer's disease (AD). MethodsNinety male SD rats of 4 months old were randomly assigned into a control group (n=10), a sham group (with injection of 1 μL normal saline into bilateral hippocampi, n=10), and a modeling group (with injection of 1 μL beta-amyloid 1-42 solution into bilateral hippocampi to induce AD, n=70). One week after modeling, 50 successfully modeled rats were selected and randomly allocated into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs once daily for six consecutive weeks. The Morris water maze was used to assess the learning and memory abilities of rats. Hematoxylin-eosin (HE) staining was performed to reveal hippocampal morphological changes in AD rats. Apoptosis in the hippocampal CA3 region was detected by terminal-deoxynucleotidyl transferase-mediated Nick end labeling. Immunofluorescence was used to visualize the expression of neuronal nuclear antigen (NeuN) in the CA1 region. Additionally, enzyme-linked immunosorbent assay was performed to assess the activities of glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase (CAT) in the hippocampus. Real-time PCR was conducted to measure the mRNA levels of Akt, GSK-3β, Nrf2, and HO-1, while Western blot was employed to determine the protein levels of phosphorylated Akt (p-Akt)/Akt, phosphorylated GSK-3β (p-GSK-3β)/GSK-3β, Nrf2, and HO-1. ResultsCompared with the control group, the model group on day 5 showed an increase in total swimming distance (P<0.01), a reduction in the percentage of time spent in the target quadrant (P<0.01), reduced and disarranged neurons, nuclear condensation, varying degrees of cellular damage, increased apoptosis of hippocampal neurons (P<0.01), decreased NeuN content (P<0.01), weakend activities of GSH-Px, GST, and CAT (P<0.01), and down-regulated mRNA levels of Nrf2 and HO-1 (P<0.01) and protein levels of p-Akt/Akt, p-GSK-3β/GSK-3β, Nrf2, and HO-1 (P<0.01) in the hippocampus. Compared with the model group, donepezil hydrochloride and high, medium, and low doses of Hei Xiaoyaosan shortened the total swimming distance on day 5 (P<0.05, P<0.01), increased the percentage of time spent in the target quadrant (P<0.05, P<0.01), improved the arrangement and morphology of neurons, reduced nuclear condensation and the apoptosis rate of hippocampal neurons (P<0.01), increased the NeuN content (P<0.01), enhanced the activities of GSH-Px, GST, and CAT (P<0.05, P<0.01), and up-regulated the mRNA levels of Nrf2 and HO-1 (P<0.05, P<0.01) and the protein levels of p-Akt/Akt, p-GSK-3β/GSK-3β, Nrf2, and HO-1 (P<0.05, P<0.01) in the hippocampus. ConclusionHei Xiaoyaosan can regulate the Akt/GSK-3β/Nrf2/HO-1 pathway to enhance the antioxidant stress capacity and inhibit neuron apoptosis to exert the neuroprotective effect, thereby ameliorating the cognitive dysfunction and pathological damage in AD rats.
3.Hei Xiaoyaosan Improves Learning and Memory Abilities in Alzheimer's Disease Rats by Regulating Cell Apoptosis
Huping WANG ; Jiao YANG ; Yiqin CHEN ; Zhipeng MENG ; Yujie LYU ; Yunyun HU ; Wenli PEI ; Yumei HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):108-115
ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease (AD) from cell apoptosis mediated by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group, a sham group, a model group, a donepezil hydrochloride (0.45 mg·kg-1) group, and high-, medium-, and low-dose (15.30, 7.65, and 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups, with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline, while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 (Aβ1-42) solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). Western blot was employed to determine the protein levels of PI3K, Akt, and NF-κB. A cell model of AD was established by co-culturing Aβ1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 (CCK-8) assay and flow cytometry (FC), respectively. ResultsAnimal experiments showed that compared with the blank group, the model group had a prolonged escape latency (P<0.01), a reduced number of crossing platforms (P<0.01), disarrangement and a reduced number of hippocampal neurons, up-regulated expression of Bax and Caspase-3, down-regulated expression of Bcl-2 (P<0.01), decreased p-PI3K/PI3K and p-Akt/Akt levels, and an increased p-NF-κB/NF-κB level (P<0.01). Compared with the model group, donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms (P<0.05, P<0.01), improved the arrangement and increased the number of hippocampal neurons, down-regulated the expression levels of Bax and Caspase-3, up-reguated the expression level of Bcl-2 (P<0.05, P<0.01), increased the p-PI3K/PI3K and p-Akt/Akt levels (P<0.05, P<0.01), and reduced the p-NF-κB/NF-κB level (P<0.05, P<0.01). Cell experiments showed that compared with the blank group, the model group exhibited an increased apoptosis rate (P<0.01). Compared with the model group, the serum containing Hei Xiaoyaosan at various doses improved the cell viability (P<0.01), and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis (P<0.01). ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis, while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.
4.Hei Xiaoyaosan Inhibits Ferroptosis by Regulating SIRT1/p53/SLC7A11 Signaling Pathway to Ameliorate Cognitive Dysfunction in Rat Model of Alzheimer's Disease
Jiao YANG ; Yiqin CHEN ; Wenli PEI ; Yumei HAN ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):116-123
ObjectiveTo investigate the effects of Hei Xiaoyaosan on cognitive impairment and the histone deacetylase sirtuin-1 (SIRT1)/tumor suppressor p53/solute carrier family 7 member 11 (SLC7A11) signaling pathway in the rat model of Alzheimer's disease (AD). MethodsA total of 90 16-week-old SPF-grade SD male rats were randomly assigned in a blank group (n=10), a sham group (n=10, with injection of 1 μL normal saline into the bilateral hippocampi), and an AD modeling group (n=70, with injection of 1 μL β amyloid 1-42 solution into the bilateral hippocampi). According to the random number table method, fifty successfully modeled rats were assigned into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, and 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups, and they were administrated with corresponding agents via gavage once a day for 42 consecutive days. Morris water maze test was carried out to examine the cognitive function of rats. Nissl staining was employed to observe the morphology of hippocampal neurons in each group, and Prussian blue staining was used to detect iron deposition in the hippocampal tissue. Biochemical kits were used to measure the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and iron ion (Fe2+) in the hippocampal tissue. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to determine the protein and mRNA levels, respectively, of SIRT1, p53, SLC7A11, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the hippocampus. ResultsCompared with the blank group, the model group showed reductions in target quadrant movement distance (P<0.01) and target quadrant residence time (P<0.05), disarrangement of hippocampal neurons, increased ferroptosis deposition in the hippocampus, a lowered level of SOD, risen levels of MDA and Fe2+ (P<0.05, P<0.01), down-regulated protein and mRNA levels of SIRT1, SLC7A11, and GPX4 (P<0.05, P<0.01), up-regulated protein and mRNA levels of p53 and ACSL4 (P<0.01), and aggravated pathological process of AD. Compared with the model group, donepezil hydrochloride extended the target quadrant residence time and the target quadrant movement distance (P<0.05, P<0.01). High- and medium- doses of Hei Xiaoyaosan extended the target quadrant residence time and the target quadrant movement distance (P<0.05, P<0.01), improved the neuron arrangement and reduced the ferroptosis deposition in the hippocampus, elevated the SOD level, lowered the MDA and Fe2+ levels (P<0.05, P<0.01), up-regulated the protein and mRNA levels of SIRT1, SLC7A11, and GPX4 (P<0.01, P<0.05), and down-regulated the protein and mRNA levels of p53 and ACSL4 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan can regulate the SIRT1/p53/SLC7A11 signaling pathway to mitigate oxidative stress and inhibit ferroptosis, thereby ameliorating the cognitive dysfunction in AD rats.
5.Construction of a prediction model for severe pneumonia complicate with respiratory failure
Siyu GAO ; Sheng ZHANG ; Xi CHEN ; Zhixia ZHANG ; Yumei YANG
Chinese Journal of Clinical Medicine 2025;32(3):449-457
Objective To explore predictive factors of severe community-acquired pneumonia (CAP) complicated with respiratory failure (RF) and to develop and internally validate a clinical prediction model. Methods A retrospective study was conducted on 350 patients with severe CAP admitted to Tianyou Hospital Affiliated to Wuhan University of Science and Technology from September 2022 to December 2024. Patients were randomly divided into a training set (n=245) and a validation set (n=105) in a 7∶3 ratio, and further categorized into RF and non-RF groups. LASSO regression was applied to optimize variable selection. Multivariate logistic analysis was used to construct the prediction model, followed by internal validation. Results Univariate regression analysis identified male, hypertension, diabetes, coronary heart disease, age, CURB-65 score, white blood cell count, neutrophil count, C-reactive protein (CRP), serum amyloid A, procalcitonin, and hospital stay as risk factors for RF in severe CAP, while albumin level was a protective factor. LASSO regression selected CURB-65 score, albumin level, and CRP for inclusion in the final model. The area under the receiver operating characteristic curve was 0.903 in the training set and 0.919 in the validation set. Calibration curve analysis demonstrated excellent agreement between predicted and observed probabilities in both sets, and Hosmer-Lemeshow goodness-of-fit tests indicated no significant deviations. Threshold probabilities ranged from 0.01 to 0.99 in both training and validation sets. Conclusions CURB-65 score, albumin level, and CRP are independent predictors of RF in severe CAP. The clinical prediction model based on these factors exhibits strong discrimination, calibration, goodness-of-fit, and clinical utility.
6.Application of repetitive transcranial magnetic stimulation in post-stroke aphasia
Journal of Apoplexy and Nervous Diseases 2025;42(4):375-379
Repetitive transcranial magnetic stimulation (rTMS) is an emerging technique for noninvasive brain stimulation and plays an increasingly important role in the rehabilitation treatment of post-stroke aphasia due to its advantages of noninvasiveness,safety,and targeting ability. With reference to related articles in China and globally in recent years,this article elaborates on the role,mechanism,and target of rTMS in post-stroke aphasia,in order to provide a reference for the rehabilitation treatment of patients with post-stroke aphasia.
Rehabilitation
7.A Critical Discussion on the Connotation of Children’s Subjectivity in Health Management
Ying DONG ; Hong XU ; Yin WANG ; Xin LIANG ; Suya YANG ; Yumei LIU ; Lili FU ; Yibo WU
Chinese Medical Ethics 2024;35(3):302-309
The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.
8.Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis
Xiaofei TANG ; Yonghong LI ; Qiuling DING ; Zhuo SUN ; Yang ZHANG ; Yumei WANG ; Meiyi TIAN ; Jian LIU
Journal of Peking University(Health Sciences) 2024;56(2):279-283
Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6%(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P<0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P<0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P<0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P<0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P<0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.
9.Case 02 (2024): Acute ST-segment elevation myocardial infarction during pregnancy caused by coronary artery dissection: a case report
Lingying KONG ; Pengkang HE ; Jianping LI ; Dongxin WANG ; Tao HONG ; Yu SUN ; Qian CHEN ; Yumei WEI ; Hong ZHANG ; Huixia YANG
Chinese Journal of Perinatal Medicine 2024;27(3):226-232
This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.
10.Stakeholder research on hospice care under the “hospital-community” coordination
Yilong YANG ; Meng CUI ; Xinxin ZHAO ; Na LI ; Yumei WANG
Chinese Medical Ethics 2024;37(3):339-346
The “hospital-community” hospice care model involves multiple stakeholders,including demander,executor,leader,and fundraiser of medical and health services.The degree of benefit correlation,policy influence,and implementation willingness of various stakeholders were analyzed to provide reference for terminal cancer patients to obtain continuous,convenient,and high-quality hospice care.Health department and medical insurance department are the main driving forces for cross-institutional hospice care,but there are differences in their driving paths.The financial department is an important guarantor of policy implementation,and needs to ensure that its core interests are not lost.Community medical institutions are an important driving factor for policy implementation,but they require policy support and hospital drive. Medical staff in hospitals and communities,have weak willingness to implement policies,which can easily become obstacles to policy implementation in the absence of incentive and compensation mechanisms.Patients and their caregivers are important beneficiaries,but lack of publicity,education,and interactive communication can also lead to rejection and contradiction.Therefore,it is necessary to leverage the collaboration and coordination between policy enforcement departments,innovate the development model of hospitals,lead community medical institutions,and promote interactive communication and decision-making sharing of “doctor-doctor” and “doctor-patient”.

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