1.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
2.Effect of modified citrus pectin on glycolysis of rabbit articular chondrocytes
Jiayue HE ; Wenlong YUAN ; Xuemin LI
International Journal of Biomedical Engineering 2024;47(1):73-81
Objective:To investigate the effect of modified citrus pectin (MCP) on the glucose metabolism of rabbit articular chondrocytes.Methods:The third generation (P3) rabbit knee chondrocytes were extracted and cultured with 0 μg/ml (MCP0, control group) and 500 μg/ml of MCP (MCP500) for 3 days. Chondrocytes (P2-P7)were cultured continuously, and each generation of chondrocytes was treated with MCP0 and MCP500 medium for 3 days. Chondrocytes were treated with interleukin-1β (IL-1β) for 1 day and then treated with MCP0 and MCP500 medium for 3 days, respectively. Chondrocytes were treated with 2-deoxy-glucose (2DG) for 1 day and then treated with MCP0 and MCP500 medium for 3 days, respectively. After three days of culture, the proliferation of chondrocytes was calculated by CCK-8. Glucose uptake activity and lactate production of chondrocytes were measured by glucose and lactate detection kits. The synthesis of type Ⅱ collagen (COL2A1) in sequential chondrocytes was investigated by immunofluorescence staining. The gene expression of COL2A1, proteoglycan ( ACAN), SOX9, hypoxia-inducible factor-1α ( HIF-1α), glucose transporter-1 ( Glut-1), pyruvate kinase M2 ( PKM2), lactate dehydrogenase-A ( LDHA) and glucose transporter-1 ( Glut-3) were further detected by RT-qPCR. Results:Compared with the control group, MCP treatment could increase the glucose uptake activity and lactate production of chondrocytes, and enhance the gene expression ability of HIF-1α, Glut-1, PKM2 and ACAN. Besides, MCP treatment could stimulate chondrocyte proliferation, maintain chondrocyte phenotype, increase lactate production, and upregulate the expression of COL2A1, ACAN, SOX9, HIF-1α, Glut-1, PKM2 and LDHA. After the treatment with IL-1β, MCP treatment could increase glucose uptake activity and upregulate the expression of COL2A1, ACAN, HIF-1α and Glut-1. After treatment with 2DG, MCP treatment could increase glucose uptake activity and upregulate the expression of SOX9, HIF-1α, PKM2 and Glut-3 genes. Conclusions:MCP can enhance the glucose uptake capacity of chondrocytes and increase the level of chondrocyte glycolytic metabolism.
3.Illness narratives and cultural implications for diabetic foot patients from the perspective of anthropology
Xiaorui SHI ; Yi’nong ZHANG ; Meng LI ; Jiayue LIU
Chinese Medical Ethics 2024;37(3):317-323
Diabetic foot is one of the common chronic complications, the most common cause of hospitalization, and even the main cause of disability and death among diabetic patients. In the process of disease occurrence, development, and treatment, patients experience complex changes in physical, psychological, and social relationships. Their understanding and practice of the disease is a constant process of construction and change, which contains strategic practices influenced by factors such as disease progression, family relationships, culture and traditions of social, and doctor-patient interactions. Based on the research concepts in the field of medical anthropology, this paper applied field research methods such as survey interviews and participatory observation, and took the rich and varied and personalized narrative of diabetic foot patients as the entry point to understand their unique and detailed disease stories, as well as focused on answering the changes in the views of illness, treatment, family, society, and the body outlook experienced by diabetic foot patients. This paper aimed to provide a new perspective for understanding this group, as well as offer valuable insights for improving their treatment and management, which will help promote the overall health and quality of life with diabetic foot patients.
4.A retrospective study on the evolution of TCM syndrome and TCM syndrome elements in the course of disease in 1,049 patients with psoriasis vulgaris
Jiayue WANG ; Ping LI ; Dongmei ZHOU ; Yanping BAI ; Xingwu DUAN ; Haibing LAN ; Yiding ZHAO ; Jingxia ZHAO ; Yan WANG ; Tingting DI ; Yujiao MENG ; Zhaoxia CHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(10):1438-1448
Objective The study aimed to elucidate the evolution of the syndromes in Traditional Chinese Medicine(TCM)and TCM syndrome elements in different chronic stages of psoriasis vulgaris.Methods A database was constructed using electronic medical records collected from July 2019 to March 2024 from 1,049 patients with psoriasis vulgaris.The study used Sankey diagrams and network association graphs to analyze the evolution of TCM syndromes and their elements in patients at the different stages:initial diagnosis,progressive stage(Week 2-3),progressive stage(Week 4-5),skin lesion improvement stage(Week 6-7),and remission stage.The syndrome elements network was constructed using community detection algorithms,and the association rules between local skin lesion syndrome differentiation and overall syndrome differentiation were displayed using heatmaps.Results(ⅰ)Initial diagnosis.In the syndrome differentiation of local skin lesions,blood heat syndrome was the most common(79.79%);among the disease location of TCM syndrome elements(called"disease location"),liver was the most prevalent(35.62%);and among the pathological factors of TCM syndrome elements(called"pathological factors"),fire(heat)was the most common(75.48%).(ⅱ)Active stage(Week 2-3).In the syndrome differentiation of local skin lesions,blood heat syndrome remained the most prevalent(73.13%);among the disease location,liver was still the most prevalent(31.71%);and among the pathological factors,fire(heat)continued to be the most common(82.11%),while dampness(22.26%)and qi stagnation(8.39%)began to increase.(ⅲ)Active stage(Week 4-5).The syndrome differentiation of local skin lesions was dominated by blood heat syndrome(45.91%)and blood dryness syndrome(37.19%);among disease location,the interior was the most prevalent(15.25%);and among the pathological factors,fire(heat)remained the most common(50.66%),with an increase in yin deficiency(34.26%).(ⅳ)Skin lesion improvement stage(Week 6-7).In the syndrome differentiation of local skin lesions,both blood dryness syndrome(49.44%)and blood stasis syndrome(33.33%)increased;among the disease location,meridians increased most significantly and became the most prevalent(13.44%);and among the pathological factors,blood stasis increased most significantly and became the most prevalent(28.20%).(ⅴ)Remission stage.In the syndrome differentiation of local skin lesions,blood stasis syndrome became the primary(55.69%),while the percentage of blood dryness syndrome decreased(21.16%);meridians(25.71%)and blood stasis(62.34%)remained the most predominant syndrome elements related to disease location or pathological factors.Conclusion The overall pattern of TCM syndromes in psoriasis vulgaris evolved from excess to deficiency.From the initial diagnosis to the active phase(Week 2-3),heat syndrome dominated;during the active phase(Week 4-5),heat syndrome coexisted with damp syndrome or yin deficiency syndrome;changes in the syndrome element network were the most significant during the lesion improvement phase,with blood stasis gradually increasing and peaking during the remission phase.Blood stasis,dampness,and qi stagnation were pervasive throughout psoriasis vulgaris;qi stagnation and blood stasis may be the main elements causing further deterioration and prolonged course of the disease during the active phase in patients.
5.Unmet needs for assistive technology and its related factors for persons with physical disabilities in Chengdu,Chi-na
Panpan CHEN ; Binglong WANG ; Liquan DONG ; Xidong LIU ; Youping YANG ; Jiayue LI
Chinese Journal of Rehabilitation Theory and Practice 2024;30(5):598-605
Objective To investigate the unmet needs for assistive technology for people with physical disabilities in Chengdu,and analyze the related factors. Methods From November,2023 to March,2024,the persons with physical disabilities in Chengdu were selected from Sichuan Individuation service platform,and investigated using World Health Organization rapid Assistive Tech-nology Assessment. Results A total of 558 questionnaires were set up,and 527 effective questionnaires retured.26.8%of them reported un-met needs for aids,with the highest need for mobility aids(66.0%).Lack of support(54.9%),high price(26.3%)and lack of knowledge about aids(20.3%)were the main reasons for not obtaining the aids they needed.Loss of spouse(OR=3.615),serious mobility impairment(OR>2.926)and serious self-care impairment(OR>2.781)were the risks of unmet needs for aids. Conclusion It is important to popularize policies and products of aids,pay attention to personal adaptation for people with different barriers,and strengthen the service system,to meet the needs of people with disabilities.
6.Clinical and genetic analysis of a Chinese patient with Alstr?m syndrome
Jiayue LI ; Jie GAO ; Lin WANG ; Yanhua LI ; Ming ZHANG ; Xietian PAN ; Xinhong GUO
Chinese Journal of Medical Genetics 2024;41(5):596-600
Objective:To explore the genetic etiology for a patient with Alstr?m syndrome (ALMS) presenting as dilated cardiomyopathy.Methods:A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis.Results:The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+ PM2_Supporting+ PM3+ PP3, PVS1_VeryStrong+ PM2_Supporting+ PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. Conclusion:The c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.
7.Discussion on hot topics and promotion paths for post-market surveillance and supervise of medical consumables based on non-active medical devices
Fang DONG ; Jianlong YANG ; Jiayue LI ; Peng NING ; Fangfang CHEN ; Shengnan SHI ; Xiaolan QIU ; Zigui XIE ; Zeshi CUI
China Medical Equipment 2024;21(2):166-173
Objective:To explore the research hotspots and effective promotion paths of post market surveillance and supervise of medical consumables with non-active medical devices.Methods:Data mining methods were used to collect related journal literatures and documents from the websites of China regulatory institutions and the China National Knowledge Infrastructure(CNKI),order sub item data of medical device adverse event reports,extract the MeSH element words of literatures and documents,perform bibliometric analysis and visual display.Results:The number of medical devices adverse event reports in China has been increasing year by year,reaching 694 866 in 2022,in the four statistical years from 2019 to 2022,the number of reports on non-active medical devices and IVD reagents also showed a parallel increasing trend,accounting for about 65.00% of the total number of adverse event reports on medical devices in the year.The bibliometric analysis of journal literature shows that research in this field has received varying degrees of participation from regulatory institutions,universities,medical institutions,and enterprises.Regulatory institutions have contributed 46 articles,accounting for 56.79% of the total number of articles,followed by 28 articles from universities.The co-occurrence analysis shows that hot topic is focused in 5 clusters:quality management,risk management,international experiences discussion and adverse event surveillance and re-evaluation and real-world research.China regulatory institutions attach great importance to post market surveillance and supervise,and have issued more than 20 relevant documents since 2006,focusing on specific topics and gradually deepening around safety and effectiveness.Conclusion:The post market surveillance and supervise of medical devices,especially medical consumables based on non-active medical devices,need to be promoted synchronously in three dimensions:regulatory institutions,medical institutions,and enterprises.Universities,research institutes,and industry organizations should work in coordinating to strengthen the collection,identification,and active surveillance of risk signals based on adverse event surveillance,safety evaluation based on risk management,and conducting real-world research,research and develop risk control and corrective and preventive measures.
8.Development and validity test of blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia
Meng LI ; Meng ZHAO ; Qian LIANG ; Jiayue LIU ; Qianqian YAO ; Zhenzhen WANG ; Bingyin SHI
Chinese Journal of Diabetes 2024;32(10):756-763
Objective To develop a blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia and test its reliability and validity.Methods The initial questionnaire was formed through literature review,expert consultation,two rounds of Delphi letter consultation,and pre-survey.From August to September 2019,a total of 125 perioperative patients with hyperglycemia who were hospitalized in the surgical ward of the First Affiliated Hospital of Xi'an Jiaotong University were selected as the survey objects by the convenient sampling method.The items of the questionnaire were screened and the reliability and validity were tested.Results A total of 125 questionnaires were distributed and 115 valid questionnaires were returned,with an effective recovery rate of 92.0%.The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia included five dimensions(17 items in total),including influencing factors and hazards of abnormal blood glucose,key points of preoperative and postoperative nursing observation,perioperative blood glucose control goals,perioperative blood glucose management points,and emergency treatment of perioperative critical conditions.The effective recovery rates for both rounds of inquiry are 100.00%,the expert authority coefficient was 0.880 and the average coefficient of variation was 0.086 and 0.065(P<0.01).Exploratory factor analysis extracted a total of five common factors,and the cumulative variance contribution rate was 79.895%.The Cronbach's α coefficient of the questionnaire was 0.905,the test-retest reliability was 0.955,and the content validity index was 0.968.Conclusions The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia is scientific and practical,which can be used as an effective tool to evaluate the blood glucose management knowledge level during perioperative period.
9.Development of the Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses and its reliability and validity
Meng LI ; Jiayue LIU ; Qian LIANG ; Meng ZHAO ; Qianqian YAO ; Bingyin SHI
Chinese Journal of Modern Nursing 2024;30(11):1450-1456
Objective:To develop the Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses and test its reliability and validity.Methods:From January to June 2019, the questionnaire item pool was constructed through literature review, and 13 experts were included in two rounds of Delphi consultation using purposive sampling. In July 2019, convenience sampling was used to select 50 clinical nurses from the surgical ward of the First Affiliated Hospital of Xi'an Jiaotong University as the research subject. A preliminary survey was conducted to form an initial Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses. From August to September 2019, 110 clinical nurses from this ward were selected as the research subject again, and the questionnaire was subjected to item screening and reliability and validity testing.Results:The final Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses included five dimensions of factors influencing blood glucose abnormalities, hazards of blood glucose abnormalities, preoperative and postoperative nursing observation points, emergency treatment of perioperative critical conditions, and key points for perioperative blood glucose management, with a total of 19 items. In the two rounds of consultation, the positivity coefficients of experts were both 100.00% (13/13), the authority coefficient of experts was 0.88, and the coefficients of variation for two rounds of consultation were 0 to 0.30 and 0 to 0.17. Exploratory factor analysis extracted five common factors, with a cumulative variance contribution rate of 66.70%. The Cronbach's α coefficient of the total questionnaire was 0.92, the test-retest reliability coefficient was 0.97, and the scale-level content validity index was 0.98.Conclusions:The Perioperative Blood Glucose Management Knowledge Questionnaire for Surgical Nurses has good scientific and practical significance, and can be used as an effective tool to evaluate the perioperative blood glucose management knowledge among surgical nurses.
10.Exploratory study on the role of tumor microenvironment-related gene CCR7 in Cuproptosis and its potential as a prognostic marker for liver cancer
Yuan CHEN ; Yunhui LI ; Jing LIANG ; Li WANG ; Renlong ZHU ; Jiayue MA ; Yajie WANG
Chinese Journal of Laboratory Medicine 2024;47(10):1169-1177
Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.

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