1.Role and Mechanism of Glucocorticoid-induced Transcription Factor 1 in Cognitive Dysfunction in Diabetic Mice
Yingrui LIU ; Jiayi WANG ; Yefeng WANG ; Jiahui LUAN ; Yun GU ; Zhongfu ZUO ; Hongdan YU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):826-835
ObjectiveTo explore the protective effect of glucocorticoid-induced transcription factor 1 (GLCCI1) on cognitive dysfunction in diabetic mice and its mechanism. MethodsTwenty-four C57BL/6J mice were randomly divided into 4 groups, namely Control, DM, DM+AAV-Glcci1, and DM+AAV-NC. The Control group was intraperitoneally injected with saline, while the other groups were all injected with streptozotocin (STZ). Two weeks after successful modeling, the DM+AAV-Glcci1 group was brain stereotactic injected with Glcci1 overexpressing adeno-associated virus, and the DM+AAV-NC group was stereoscopically injected with the control virus. After 12 weeks, the Morris water maze test was used to evaluate the learning and memory abilities of mice in each group. Subsequently, the localized expression of GLCCI1 in the hippocampus were determined by immunofluorescence and immunohistochemistry experiments. The myelin morphology in the hippocampus was observed by LFB staining, the neuronal morphology was observed by Nissl staining, and the myelin-related proteins MBP and CNPase were stained by immunohistochemistry. Molecular docking was used to predict the interaction between GLCCI1 and HSPA5. The expression of endoplasmic reticulum stress-related proteins was detected by Western blot. ResultsThe results of the behavioral experiment showed that compared with the mice in the Control group, DM mice exhibited obvious cognitive dysfunction behaviors (P<0.000 1), and the learning and memory abilities of mice improved after overexpression of Glcci1 (P=0.000 7). The results of immunofluorescence and immunohistochemistry showed that GLCCI1 was expressed in hippocampal neuron cells. Compared with Control mice, the expression level of GLCCI1 in DM mice was significantly downregulated (P<0.000 1). The molecular docking results revealed that GLCCI1 interacts with HSPA5. The Western blot results indicated that, compared with the Control group, the expression levels of endoplasmic reticulum stress-related proteins HSPA5 (P<0.000 1), ATF4 (P<0.000 1), ATF6 (P=0.001 1), and p-ELF2α/elF2α (P=0.000 1) in the DM group were significantly increased; Compared with the DM group, the expression of the corresponding protein HSPA5 (P<0.000 1), ATF4 (P<0.000 1), ATF6 (P=0.000 2), and p-ELF2α/elF2α (P=0.000 1) was significantly down-regulated after overexpression of Glcci1. LFB staining showed that compared with the Control group, the myelin integrity of DM mice decreased significantly (P=0.010 3), the expressions of myelin-related proteins MBP and CNPase decreased significantly (P=0.000 4, P=0.000 2), and Nissl staining observed disordered neuronal arrangement. Compared with the mice in the DM group, the myelin integrity in the hippocampal region significantly increased after overexpression of Glcci1 (P=0.000 3), the expressions of myelin-related proteins MBP and CNPase significantly increased (P=0.001 4, P=0.000 1), and the ordered arrangement of neurons was observed by Nissl staining. ConclusionThe down-regulation of GLCCI1 expression in hippocampal neurons promotes demyelination of hippocampal neurons and thereby induces diabetic cognitive dysfunction. The specific mechanism may be related to endoplasmic reticulum stress.
2.Discussion on the pathogenesis of pan-vascular diseases based on the theory of"stagnation due to qi deficiency"
Sixiang ZHANG ; Zheng LIU ; Youmin ZHAO ; Yuhan LI ; Yixuan LI ; Yingrui WANG ; Qinyu ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):983-988
Pan-vascular medicine is an emerging discipline focusing on atherosclerotic diseases,with the concept of multidisciplinary integration,emphasizing on exploring the mechanism of disease development from the whole of the organism's structure and function.At present,the basic mechanism system of pan-vascular diseases has yet to be perfected.The pan-vascular concept is highly compatible with the idea of Chinese medicine that focuses on the overall view.Deficiency of all qi is the root cause of pan-vascular diseases,while phlegm,blood stasis,and water-dampness and other tangible evils stagnate in the veins and channels as the symptoms of the disease,therefore,the disease mechanism can be highly summarized as"stagnation due to qi deficiency".Deficiency leads to the stagnation,blocking the veins and channels,and the deficiency worsens due to the stagnation and then damages the veins and channels,thus,it develops into a disease.Based on the theory of"stagnation due to qi deficiency",this paper takes endothelial cell dysfunction as the entry point of pan-vascular diseases,and considers that low endothelial cell immunity is the initiating factor of pan-vascular diseases,and that the widespread persistence of microinflammatory state is the key pathology to pan-vascular diseases.
3.Single-cell and spatial heterogeneity landscapes of mature epicardial cells
Jianlin DU ; Xin YUAN ; Haijun DENG ; Rongzhong HUANG ; Bin LIU ; Tianhua XIONG ; Xianglin LONG ; Ling ZHANG ; Yingrui LI ; Qiang SHE
Journal of Pharmaceutical Analysis 2023;13(8):894-907
Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.
4.Qualitative study on the medical experience and staged care needs of patients undergoing ophthalmic ambulatory surgery
Dandan JING ; Ning LI ; Yan LIU ; Yingrui YANG
Chinese Journal of Modern Nursing 2023;29(6):810-814
Objective:To explore the medical experience and staged care needs of patients undergoing ophthalmic ambulatory surgery.Methods:In this qualitative study, 21 ophthalmic ambulatory surgery patients from Henan Provincial Ophthalmology Hospital were selected by purposive sampling for semi-structured in-depth interviews from February to June 2022, and the content of the interviews was analyzed by Colaizzi's analysis.Results:A total of 4 first-level themes were extracted from the content analysis, including medical experience, preoperative preparation-related information needs, nursing needs for postoperative complications, and home rehabilitation nursing and follow-up needs. Among them, the medical experience included saving time for medical treatment, insufficient preoperative preparation, and anxiety.Conclusions:For ophthalmic ambulatory surgery patients, it is necessary to strengthen information support, provide targeted health education for ambulatory surgery, provide psychological and emotional support, and further improve the postoperative rehabilitation management process to enhance the quality of nursing services for ambulatory surgery.
5.Study on the modeling method and pathological parameters of chronic atrophic gastritis
Miaomiao YIN ; Huiyun LIU ; Jianliang SUI ; Yajun QIAO ; Yingrui TIAN ; Menglei WANG ; Zhen WANG
Chinese Journal of Digestion 2021;41(Z1):54-60
Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.
6.Consistency of continuous glucose monitoring system and scanning blood glucose monitoring system in predicting dawn phenomenon in patients with type 2 diabetes mellitus
Mingnan LI ; Zhiling ZHU ; Xiaoxia FANG ; Zhiqiang LIU ; Xiao WU ; Weijuan SONG ; Yingrui WANG ; Zhifang WANG
Chinese Journal of Modern Nursing 2021;27(9):1181-1185
Objective:To investigate the effectiveness of scanning glucose monitoring system in dawn phenomenon of patients with type 2 diabetes mellitus (T2DM) based on continuous glucose monitoring system (CGMS) .Methods:A total of 45 patients with T2DM hospitalized in the Endocrine Department of Xinxiang Central Hospital from June 2019 to June 2020 were selected as the research subjects by convenience sampling method. All selected patients were asked to wear the scanning glucose monitoring system after admission, and then the CGMS for continuous glucose monitoring after 48 hours. The scanning glucose monitoring system and the CGMS were taken off at the same time after 72 hours. The blood glucose analysis report of the same period was checked to determine whether the dawn phenomenon occurred. The consistency to determine dawn phenomenon was analyzed between CGMS and scanning blood glucose monitoring by Kappa test. According to the CGMS judgment results, the receiver operating characteristic curve (ROC) of the scanning blood glucose monitoring system was drawn to evaluate the optimal tangent value of the night blood glucose for predicting dawn phenomenon and the next day fasting blood glucose for evaluating dawn phenomenon.Results:Among the 45 study subjects, there was no statistical difference in determining the incidence of dawn phenomena between CGMS and scanning glucose monitoring system [55.56% (25/45) vs. 46.67% (21/45) , χ 2=0.711, P>0.05]. Consistency analysis showed that Kappa value was 0.895, and the consistency of CGMS and scanning glucose monitoring system in judging dawn phenomenon was good (Kappa=0.895, 95% CI 1.130-4.883, P<0.01) . The optimal tangent value of night blood glucose for predicting dawn phenomenon was 8.31 mmol/L, and the optimal tangent value of the next day fasting blood glucose for evaluating dawn phenomenon was 7.25 mmol/L. The value of the area under the ROC curve were 0.729 and 0.803 respectively. Conclusions:Scanning blood glucose monitoring can accurately judge the dawn phenomenon. When the night blood glucose value is 8.31 mmol/L, it indicates that the dawn phenomenon may occur. When the next day's fasting blood glucose value is 7.25 mmol/L, it indicates that the dawn phenomenon may already occur.
7.Effect of body mass index on patients with rectal cancer undergoing laparoscopic total mesorectal excision
Peizhe LI ; Xukun LYU ; Hengling GAO ; Yingrui HEI ; Xishan LIU
Chinese Journal of Postgraduates of Medicine 2019;42(1):6-9
Objective To study the safety and short-term clinical outcome of different body mass index (BMI) patients with rectal cancer undergoing laparoscopic total mesorectal excision (TME). Methods The clinical data of 179 rectal cancer patients who had underwent laparoscopic TME from November 2016 to November 2017 were retrospectively analyzed. The patients were divided into 3 groups according to the BMI:leanness group (BMI<18.5 kg/m2, 15 cases), normal group (BMI 18.5 to 22.9 kg/m2, 89 cases) and overweight/obesity group (BMI ≥23.0 kg/m2, 75 cases). The general clinical data and the operation-related situation were compared. Results The rate of preoperative complications in overweight/obesity group was significantly higher than that in leanness group and normal group: 45.33%(34/75) vs. 4/15 and 28.09%(25/89), the preoperative albumin level in leanness group was significantly lower than that in normal group and overweight/obesity group:(36.3 ± 2.8) g/L vs. (38.6 ± 3.2) and (39.1 ± 3.7) g/L, and there were statistical differences (P<0.05). The operation time and blood loss in overweight/obesity group were significantly higher than those in leanness group and normal group: (149.2 ± 32.9) min vs. (129.3 ± 28.7) and (133.5 ± 23.6) min, (135.5 ± 29.0) ml vs. (117.5 ± 22.6) and (122.5 ± 25.9) ml, and there were statistical differences (P<0.05). There were no statistical differences in sex, age, tumor location, tumor maximum diameter, depth of tumor invasion, lymph node metastases, surgical approach, circumferential margin, number of lymph node dissections, length of resected specimens, incidence of postoperative complications, surgical site infection, postoperative urinary retention, postoperative exhaust time and postoperative hospitalization among 3 groups (P>0.05). Conclusions The differences of BMI mean different complications and nutritional status of patients. Overweight and obesity can lead to difficult operation of laparoscopic TME, but do not affect the radical cure of operations and the safety of clinical outcomes.
8.Effects of Xiezhuo Jiedu Decoction on expression of IL-10,TNF-?and NF-?B in ulcerative colitis rats
Jianquan CHEN ; Jianping LIU ; Xiaomeng LANG ; Yingrui RONG
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(03):-
Objective:To observe the effects and mechanism of Xiezhuo Jiedu Decoction on the expression of IL-10,TNF-? and NF-?B in ulcerative colitis rat.Methods:2,4,6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution was administrated by enema to establish ulcerative colitis rats models.Five groups were set up in the experiments:normal control group,model control group,salazosulfamide group,Xiezhuo Jiedu Decoction low-dose group,Xiezhuo Jiedu Decoction high-dose group;Pathomorphological observation was carried out on the rats'colon(DAI scores and CMDI scores).Cytokines IL-10,TNF-? were determined by radioimmunoassay;NF-?B p65 was determined by immunohistochemical staining(SP method).Results:Xiezhuo Jiedu Decoction can significantly reduce the CMDI sores of the rats'colon and the expression of NF-?B p65,increase the content of IL-10,decrease the content of TNF-?.Conclusion:Xiezhuo Jiedu Decoction had good therapeutic effect on ulcerative colitis in rats,its mechanism may be related to reducing the expression of NF-?B p65,increasing the content of IL-10,decreasing the content of TNF-?.
9.Expression of Egr-1 gene in human hepatocellular carcinoma tissues
Miaowang HAO ; Yanfang LIU ; Yingrui LIANG ; Mingyao WU ; Huanxing YANG ; Xianying WU
Chinese Journal of Clinical and Experimental Pathology 2001;(1):49-52
To investigate the role of Egr-1 in the carcinogcnestic process of hepatocellular carcinoma (H-CC). Methods Expression of Egr-1 gene in HCC tissues were detected by in situ hybridization and immunohistochemistry. Human breast andmouse liver and brain tissues were used for control. ResultsLittle or no Egr-1 transcription was detected both in HCC tissues and in their normal counterparts. High transcription of Egr-1 was detected in the LCD and atrophic-like liver plate of HCC tissues. Protein expression of Egr-1 gene was consistent with mRNA transcription. High expression of Egr-1 protein was also detected in normal breast and mouse brain tissues. ConclusionsLittle or no expression of Egr-1 may play a role in the deregulation of normal growth in the carcinogenestic process of HCC. The differences of Egr-1 expression among liver cells, breast epithelia and mouse brain tissues might be associated with their different ways of proliferation and differentiation in different cell types.
10.Synergy of taxol combined with irradiation on apoptosis induction in human nasopharyngeal carcinoma cell line
Weixiong LI ; Yanhui LIU ; Yingrui CHEN
Chinese Journal of Radiation Oncology 1995;0(02):-
Objective To study the synergistic effect of taxol and irradiation on programmed cell death induction in the human nasopharyngeal carcinoma cell line (CNE) in vitro.Methods Cell viability was evaluated by clonogenic assay. Cell cycle perturbation was assessed by flow cytometric analysis and apoptosis was determined with TUNEL.Results The intensity of cytotoxicity depended on the taxol dose used to CNE cells during the first 24 hrs. A G 2+M block was present with exposure to the drug of 100 nmol/L. When CNE cells were irradiated after 24 hrs of taxol exposure, synergistic effect was demonstrated with a taxol SER of 1.23. The same level apoptosis was induced by 10 ?mol/L taxol for 24 hrs or 2 Gy X-ray radiation in CNE cells.By both,the increase of induced apoptotic cells was over their additive results. Conclusion Taxol combined with radiation is able to enhance the radiosensitivity in the CNE cell line.

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