1.Molecular Crosstalk Mechanisms of Shoutai Wan and Juyuan Jian on Maternal-fetal Interface Subcellular Clusters in CBA/J×DBA/2 Recurrent Pregnancy Loss Model
Jingxin GAO ; Qiuping CHEN ; Xiaoyan ZHENG ; Pengfei ZENG ; Rui ZHOU ; Yancai TANG ; Qian ZENG ; Wenli GUO ; Jinzhu HUANG ; Weijun DING ; Linwen DENG ; Hang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):70-87
ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss (RPL) by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus (Shoutai Wan, Juyuan Jian)-of traditional Chinese medicine (TCM) at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c (blank group) and DBA/2 (modeling group) mice separately. Pregnant mice in the modeling group were randomly grouped as follows: high/low-dose Shoutai Wan, high/low-dose Juyuan Jian, model (RPL), and positive control (dydrogesterone), with 10 mice in each group. Starting from the day after the detection of the vaginal plug, mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention, the following indicators were measured. ① Macroscopic evaluation: general conditions, uterine wet weight, embryo loss rate, four coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], and peripheral blood estradiol (E2) and progesterone (Pg) levels. The decidua with embryos was stained with hematoxylin-eosin (HE) and evaluated by transmission electron microscopy (TEM). The expression of B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), angiotensin Ⅱ (AngⅡ), matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), CXC chemokine ligand 12 (CXCL12), and microtubule-associated protein 1 light chain 3 homolog (LC3)Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level: The decidua with embryos from the blank, model, high-dose Shoutai Wan, and high-dose Juyuan Jian groups (6 mice per group, with 3 single-cell samples per group, totaling 24 mice) were analyzed by the BD Rhapsody™ platform, and the whole-cell atlas was drawn by uniform manifold approximation and projection (UMAP) dimensionality reduction clustering combined with the single-cell mouse cell atlas (scMCA). The differentially expressed genes (DEGs) and cell interaction networks were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat, and the protein-protein interaction (PPI) map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells (natural killer cells, NK cells) from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group, the RPL group showed an increase in the embryo loss rate (P<0.01), down-regulated expression of Bcl-2, LIF, MMP-2, and Vegf in the decidua with embryos (P<0.05), up-regulated protein levels of CXCL-12, AngⅡ, and IL-6 (P<0.05), blocked angiogenesis, apoptosis-inflammation imbalance, and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance, and Shoutai pill showed superior performance in restoring the E2 level to the Pg level (P<0.05). ② Single-cell transcriptome analysis indicated that compared with the blank group, the RPL group showed differences in multiple key cell populations such as decidual cells, trophoblast cells, endothelial cells, erythroblasts, NK cells, and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group, high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer (upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes) and macrophages (upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes) through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins, cell adhesion, and programmed cell death, thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells (up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes) and macrophages (up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes), which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D, CDH5, GDF, and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 (STAT3) and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7, a decreased proportion of reparative dNK4, and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1, thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method (Shoutai Wan) has an advantage in regulating the phenotypes of unfolded protein, cell adhesion, and programmed cell death, and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method (Juyuan Jian) has an advantage in regulating epithelial-mesenchymal transition (EMT), angiogenesis, and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.
2.Effect evaluation of pharmaceutical service based on root cause analysis combined with KAP theory on decreasing the protocol violations of investigational medicinal products rate in pediatric clinical trials
Chunyan GUO ; Yi ZHANG ; Yuxin YANG ; Yuguang LIANG ; Qian DING ; Qian WANG ; Chengyue ZHANG ; Yu SUN ; Peng GUO
China Pharmacy 2026;37(9):1206-1210
OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis (RCA) in a problem-oriented manner combined with knowledge-attitude-practice (KAP) theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group, and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials, while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge, attitude and practice on the basis of routine pharmaceutical services, according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products, as well as the incidences of minor and major protocol violations, were all significantly lower in the observation group than in the control group ( P <0.001). The main types of protocol violations in both groups included missed/under-/over-dosing of medications, non-adherence to administration time, failure to adjust dosage as required, and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations, the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group ( P <0.001, P <0.001, P =0.025). However, there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups ( P >0.05). CONCLUSIONS Pharmaceutical services led by pharmacists, based on problem-oriented RCA and combined with KAP theory, can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials, thereby safeguarding the safety and rights of study participants.
3.Effect of Heat-sensitive Moxibustion on Quality of Life and Immune Function in Non-Small Cell Lung Cancer Patients with Qi Deficiency and Phlegm Stasis Syndrome Undergoing Chemotherapy:A Randomized Controlled Trial
Wenhao ZHAN ; Qian DING ; Zhiwei DONG ; Ting LI ; Shumei FU ; Ning TIAN
Journal of Traditional Chinese Medicine 2026;67(12):1289-1296
ObjectiveTo observe the effect of heat-sensitive moxibustion on quality of life and immune function in non-small cell lung cancer (NSCLC) patients undergoing chemotherapy. MethodsSeventy NSCLC patients with qi deficiency and phlegm stasis syndrome were randomly divided into an intervention group and a control group, with 35 cases in each group. The control group received chemotherapy combined with routine symptomatic treatment, while the intervention group additionally received heat-sensitive moxibustion since the first day of chemotherapy. Acupoints included Dazhui (GV14), bilateral Feishu (BL13), Zhongwan (CV12), Qihai (CV6), and Guanyuan (CV4). The site exhibiting the strongest heat-sensitization response was selected for moxibustion. Treatment was administered for 45 minutes per session, three times weekly for three consecutive weeks, totaling nine sessions. Before and after treatment, quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and traditional Chinese medicine (TCM) syndrome scores were evaluated. Peripheral blood levels of natural killer (NK) cells and T-lymphocyte subsets including CD3+, CD4+, and CD8+, and CD4+/CD8+ ratio were measured. Levels of programmed cell death protein-1 (PD-1), including PD-1⁺CD4⁺ and PD-1⁺CD8⁺ cells, were also assessed. Liver and renal function were monitored before and after treatment, and adverse events were recorded. ResultsIn the intervention group, 1 participant withdrew and 1 was excluded, while in the control group, 2 participants withdrew. Ultimately, 33 participants in each group were included in the final analysis. The intervention group showed significant improvements in physical, role, emotional, cognitive, and social functioning, as well as global health status after treatment, while scores for fatigue, nausea and vomiting, dyspnea, appetite loss, diarrhea, and TCM syndrome scale were significantly decreased (P<0.05). Moreover, the intervention group demonstrated higher scores in physical functioning, role functioning, and global health status, as well as lower scores for fatigue, nausea and vomiting, dyspnea, appetite loss, diarrhea, and the TCM syndrome scale than the control group (P<0.05). After treatment, the levels of peripheral NK cells and PD-1⁺CD8⁺ T cells in the intervention group increased significantly; furthermore, the intervention group exhibited higher peripheral NK cell levels and lower PD-1⁺CD8⁺ T cell levels than the control group (P<0.05). No significant differences were found in liver or renal function between the two groups (P>0.05). In addition, no adverse events such as burns or moxibustion-induced syncope occurred during the study. ConclusionHeat-sensitive moxibustion as an adjunctive therapy may enhance immune function, alleviate clinical symptoms, and improve quality of life, while demonstrating a favorable safety profile in NSCLC patients with qi deficiency and phlegm stasis.
4.Application of Gas Chromatography Ion Mobility Spectrometry Technology Combined with Chemometric Methods in Identification of Foeniculi Fructus from Haiyuan Region
Xiurong TIAN ; Hao WANG ; Kejing PANG ; Penglong YU ; Xia LIU ; Mengyue SHEN ; Xianglin JIANG ; Yonghua LI ; Zhihong LI ; Hongqiong DING ; Qin YANG ; Xingying LI ; Qian XIONG ; Guochao WAN ; Yuexiang MA ; Zhenping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):184-192
ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan, providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas, including Minqin (Gansu), Bozhou (Anhui), Qingdao (Shandong), Dezhou (Shandong), Urumqi (Xinjiang), Nujiang (Yunnan), Gutuo (Inner Mongolia), and Haiyuan (Ningxia). Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect the volatile organic compounds (VOCs) in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology (NIST) mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform, VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted, and 97 VOCs detected via GC-IMS were subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection (VIP) values greater than 1. ResultsA total of 97 VOCs were identified, including alcohols, aldehydes, ketones, esters, organic acids, terpenoids, ethers, alkenes, and benzenes. The PLS-DA model, based on VOCs data obtained by GC-IMS, effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation, the model achieved a prediction parameter (Q2) of 0.976 and a goodness-of-fit parameter (R2) of 0.936, with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology, PLS-DA, and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.
5.Application of Gas Chromatography Ion Mobility Spectrometry Technology Combined with Chemometric Methods in Identification of Foeniculi Fructus from Haiyuan Region
Xiurong TIAN ; Hao WANG ; Kejing PANG ; Penglong YU ; Xia LIU ; Mengyue SHEN ; Xianglin JIANG ; Yonghua LI ; Zhihong LI ; Hongqiong DING ; Qin YANG ; Xingying LI ; Qian XIONG ; Guochao WAN ; Yuexiang MA ; Zhenping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):184-192
ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan, providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas, including Minqin (Gansu), Bozhou (Anhui), Qingdao (Shandong), Dezhou (Shandong), Urumqi (Xinjiang), Nujiang (Yunnan), Gutuo (Inner Mongolia), and Haiyuan (Ningxia). Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect the volatile organic compounds (VOCs) in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology (NIST) mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform, VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted, and 97 VOCs detected via GC-IMS were subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection (VIP) values greater than 1. ResultsA total of 97 VOCs were identified, including alcohols, aldehydes, ketones, esters, organic acids, terpenoids, ethers, alkenes, and benzenes. The PLS-DA model, based on VOCs data obtained by GC-IMS, effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation, the model achieved a prediction parameter (Q2) of 0.976 and a goodness-of-fit parameter (R2) of 0.936, with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology, PLS-DA, and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.
6.Detection, exposure characteristics, and health risks of microplastics in human body: Progress and perspectives
Journal of Environmental and Occupational Medicine 2025;42(8):978-986
Microplastics have been identified as one of the four major emerging global pollutants, with its associated health risks becoming a forefront scientific issue in the fields of public health and ecological safety. Large amounts of microplastics have been detected in various environmental media, food products, and daily-use commodities which are in frequent contact with humans. Three primary pathways of human exposure to microplastics are inhalation, ingestion, and dermal contact. Current available studies have revealed that microplastics with diverse morphologies and dimensions have been identified in many human biological samples, including blood, liver, and placenta by spectroscopic and mass spectrometric techniques. However, the potential implications of microplastics on human health remain largely undefined. This review summarized and compared the exposure levels, size distributions, morphological characteristics, and chemical compositions of microplastics in different human tissues and organs. It also summarized current common analytical techniques for detecting microplastics in human biological samples, and analyzed the potential adverse effects of microplastic deposition on human tissues and organs. Finally, the limitations of current research were discussed, and a prospective outlook was provided on how to scientifically and effectively conduct investigation of microplastics in human populations.
7.Influencing factors of overweight and obesity among primary and secondary school students in Pudong New Area of Shanghai
Mengyuan DING ; Ling HUANG ; Qian WU ; Chao LIANG ; Yuxin JIANG ; Chunhua GU
Journal of Public Health and Preventive Medicine 2025;36(6):142-146
Objective To investigate the status and influencing factors of overweight and obesity among primary and secondary school students in Pudong New Area of Shanghai, and to provide reference for formulating obesity-related intervention strategies for school-age children. Methods Stratified cluster random sampling method was used to conduct a questionnaire survey among primary and secondary school students in Pudong New Area. The overweight and obesity rate was calculated according to the Chinese health industry standard, and the risk factors of overweight and obesity in children and adolescents of different school age groups were analyzed by logistic regression. Results The overweight and obesity rate (25.3%) of primary and secondary school students in Pudong New Area exceeded the national average level. In primary school group, male, sleep time ≥ 8h per day, water intake ≥ 1200 mL per day, and the presence of mobile food stalls around the school were the risk factors for overweight and obesity. Daily extracurricular exercise time of 30 minutes to 2 hours was a protective factor. In junior high school group, male and electronic product use time of ≥ 2h per day were the risk factors for overweight and obesity. The daily extracurricular exercise time of 1 to 2 hours was a protective factor. In high school group, drinking water ≥1200mL per day was a risk factor for overweight and obesity. Eating breakfast every day for the past week was a protective factor. Conclusion Group intervention targeting overweight and obese school-age children, while changing corresponding unhealthy habits according to different school age groups, is crucial for weight loss in school-age children.
8.Time series analysis of key genes and identification of signaling pathways in skeletal muscle inflammation after high-load exercise
Yan ZHANG ; Longyu LIANG ; Yu XIA ; Yan QIAN ; Haili DING
Chinese Journal of Sports Medicine 2025;44(1):29-43
Objective To examine the time window effect of high-load exerciseon skeletal muscle in-flammation genes,and identify the key genes and signaling pathways involved in this process.Methods Forty-eight Sprague-Dawley rats were randomly assigned to a control group(group C,n=8)and an ex-ercise group(group E,n=40).Gastrocnemius muscles were collected immediately(group E0),12h(group E12),24h(group E24),48h(group E48),and 72 h(group E72)after exercise for transcrip-tome sequencing.Differentially expressed genes(DEGs)were identified,and enrichment analysis was carried out using the Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)annotations.Meanwhile,inflammation-related genes were obtained from databases,and differ-entially expressed inflammation-related genes(DEIRGs)were done through identifying their intersec-tion with DEGs.Moreover,the Mfuzz algorithm was used for time series clustering to obtain subsets with similar characteristics.GO and KEGG analyses,along with protein interaction network analysis,were performed to obtain key DEIRGs,followed by secondary functional enrichment to analyze changes in expression of key genes over time and identify key signaling pathways.Results Seven DEIRG clus-ters were obtained through Mfuzz time series clustering of skeletal muscle inflammation genes after high-load exercise.Overall,the expression of DEGs in cluster 5 was downregulated,while that in cluster 7 was upregulated.The expression of DEGs in clusters 3 and 4 was upregulated at E0 and rap-idly downregulated at E12.In contrast,the expression of DEGs in cluster 2 and 6 were downregulated at E0 and rapidly upregulated at E12.The expression of DEGs in cluster 1 was upregulated at E0,rapidly downregulated at E12,and remained upregulated at E24.Screening identified TP53,STAT3,CD44,AKT1,KDR,GJA1,CYCS,HIF1A,IQGAP3,FASN,and TFRC as key DEIRGswhich were enriched in apoptosis,HIF-1,apoptosis,ferroptosis,MAPK,VEGF,PI3K-Akt,insulin resistance,FoxO,AMPK and the JAK-STAT signaling pathway.Conclusion Inflammation-related genes exhibit temporal dynamic changes in exercise-induced muscle damage and show significant time window effects at 12 h after exercise.The key targets STAT3,AKT1 and HIF-1A react to exercise-induced muscle damage through the JAK-STAT,PI3K-Akt,HIF-1 and VEGF signaling pathways,and promote tissue repair.
9.Gait symmetry in patients with functional ankle instability-based on vector coding technology
Qian-feng MA ; Li LI ; Jian DING
Chinese Journal of Rehabilitation Medicine 2025;40(9):1373-1379
Objective:To explore gait symmetry of unilateral functional ankle instability(FAI).Method:Fifteen male subjects with right functional ankle instability were recruited,Qualisys was used to col-lect and intercept gait cycle data on both sides.Coupling angle and standard deviation of the coupling angle were calculated using Matlab and the effect size was evaluated using Cohen's d.Result:①The coupling angles of the healthy side and the affected side were different in the sagittal plane.The average coupling angles of the hip-knee joint and the hip-ankle joint were higher on the healthy side than on the affected side in the pre-swing period(P<0.05,d=1.02;d=1.11);The average coupling angle of the knee to ankle was higher in 50%of the healthy side than the affected side after the end of support(P<0.05,d=1.21),higher in the pre-swing stage than in the affected side(P<0.05,d=1.07),and lower in 25%—50%of the healthy side during the swing stage than in the affected side(P<0.01,d=1.51).②The coupling angle between the healthy side and the affected side was different in the coronal plane only between the hip and an-kle joint,that is,the healthy side was higher than the affected side in the pre-swing stage(P<0.05,d=1.07)and the healthy side was higher than the affected side in the last part of the gait swing stage(P<0.05,d=1.06).③The standard deviation of coupling angle of sagittal plane of healthy side was lower than that of af-fected side(P<0.01),and the standard deviation of coupling angle of coronal plane of healthy side was high-er than that of affected side(P<0.01).Conclusion:①In patients with functional ankle instability,the coordination pattern of the affected side was mainly in the same pattern of proximal sagittal domination and the reverse pattern of distal coronal domina-tion,that is,the dominance of the ankle joint increased,while the dominance of the hip and knee joint de-creased.②The lower or higher variability of knee-ankle joint in sagittal plane or hip-ankle joint in coronal plane respectively than that of healthy side suggest that ankle joint on the affected side has lower gait adapt-ability,resulting in gait asymmetry and increasing the risk of ankle joint injury.③Based on the above re-sults,it is suggested that future rehabilitation therapy should focus on strengthening the strength of the knee extensor and abductor muscles of the affected hip,improving the symmetry of the left and right gait of unilat-eral FAI,and reducing the risk of recurrent injury in patients with ankle instability.
10.Role of GLUT1-dependent glycolysis in attenuation of oxygen-glucose deprivation-reoxygenation injury by dexmedetomidine in HK-2 cells
Wei DING ; Wen-hui TAO ; Yu-le WU ; Jian-xiao WU ; Jing-yi GUO ; Li-fang XIE ; Bing-qian FAN ; Xue-song GU ; Yang LI ; Xian-wen HU
Chinese Pharmacological Bulletin 2025;41(3):444-450
Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P<0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P<0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P<0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P<0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.


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