1.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
2.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
3.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
4.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
5.YAN Huimin's Experience in Staged Treatment of Pediatric IgA Vasculitis
Tianxiang LIU ; Qian ZHAO ; Jing HAO ; Mengtong WANG ; Jiayi LIU ;
Journal of Traditional Chinese Medicine 2025;66(12):1212-1216
This paper summarizes Professor YAN Huimin's clinical experience in the staged treatment of pediatric IgA vasculitis. It is believed that the pathogenesis in the acute stage is characterized by fire and heat entering the blood and damaging the collaterals, and the treatment should focus on clearing heat and stopping bleeding, using the self-formulated Qingzi Liangxue Formulation (青紫凉血方). In the remission stage, the pathogenesis is qi rebellion leading to blood extravasation. The treatment principle is to regulate qi and stabilize blood, using the self-formulated Heqi Ningxue Formulation (和气宁血方). During the protracted stage, the pathogenesis is latent pathogenic factors due to yin deficiency, and the treatment should aim to nourish the collaterals and strengthen the root, with the self-formulated Yangluo Guben Formulation (养络固本方). Meanwhile, the method of promoting blood stasis resolution is consistently applied throughout the entire treatment process.
6.Cross lagged analysis of anxiety and depressive symptoms,uncertainty stress with academic buoyancy in college students
LIU Yuxuan, WANG Yuhao, WANG Yihan, WANG Yingxue, HU Xinyi, TIAN Susu, TIAN Jiayi, WANG Wei
Chinese Journal of School Health 2025;46(6):832-836
Objective:
To examine the reciprocal relationships of anxiety and depressive symptoms,uncertainty stress with academic buoyancy among college students, providing evidence for mental health promotion and academic resilience enhancement.
Methods:
A multi stage cluster random sampling method was used to selected 741 undergraduates from grade 1 to 2 of a university in Xuzhou, Jiangsu Province. Participants completed two waves of surveys (T1: October 2022; T2: October 2023) using the Uncertainty Stress Scale, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Academic Buoyancy Scale. Cross lagged models analyzed bidirectional relationships between three mental health variables and academic buoyancy, followed by latent variable modeling integrating all mental health dimensions.
Results:
Cross lagged model results revealed that T1 uncertainty stress negatively predicted T2 academic buoyancy ( β =-0.14), while T1 academic buoyancy negatively predicted T2 uncertainty stress ( β =-0.11); T1 depressive symptom negatively predicted T2 academic buoyancy ( β =-0.08), while T1 academic buoyancy negatively predicted T2 depressive symptom ( β =-0.09); furthermore, T1 academic buoyancy negatively predicted T2 anxiety symptom( β =-0.10) ( P <0.05). Results from the latent variable cross lagged model of psychological problems (constructed from the three mental health variables) indicated that T1 psychological problems negatively predicted T2 academic buoyancy ( β =-0.09), while T1 academic buoyancy negatively predicted T2 psychological problems ( β =-0.09) ( P <0.05).
Conclusions
Longitudinal bidirectional relationships exist between mental health status and academic buoyancy in college students. Better mental health facilitates higher academic buoyancy.
7.Evaluation of the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators
Zhibin ZHANG ; Bin BAI ; Hailiang LI ; Jie YAO ; Lantao LIU ; Jiayi MA ; Yongzhong MA
Chinese Journal of Radiological Health 2025;34(4):546-552
Objective To evaluate the current status in the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators, identify issues in the application of its technical indicators, and provide a basis for the in-depth implementation and further revision of the standard. Methods In accordance with the Standardization Law of the People’s Republic of China and the Guidelines for Health Standards Tracking Evaluation (WS/T 536-2017), a combination of cluster sampling and stratified sampling methods was employed to select professionals involved in proton accelerator radiotherapy devices and facilities in three provinces (or municipalities directly under the central government) as the subjects of the survey. A questionnaire was developed to collect basic information about the subjects and their understanding and application of the technical indicators in the standard. A standard evaluation indicator system with a total score of 100 points was established to score the implementation of the standard (40 points), the technical content (30 points), and the effectiveness of the implementation (30 points). Results A total of 169 professionals from 107 institutions participated in the survey, with 79.88% of the respondents having at least 5 years of experience in radiation therapy and 74.56% holding intermediate or higher professional titles. The score of standard implementation was 18.3 points. The awareness rate exceeded 80%, indicating a high level of awareness about the standard. However, the scores for the dissemination and application of the standard were relatively low, accounting for 28% and 32% of their respective full marks. The technical content of the standard and the effectiveness of its implementation scored 27.0 and 26.6 points, respectively. The overall score in the evaluation of standard implementation was 72 points, with scores of 68.6, 72.3, and 75.0 for Beijing City, Shanghai City, and Jiangsu Province, respectively. Conclusion GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators is scientific and operable, and it is well-coordinated with relevant laws and standards. However, considering the development in FLASH technology and multi-chamber radiotherapy room, it is necessary to revise and improve the standard.
8.A lung cancer early-warning risk model based on facial diagnosis image features
Yulin Shi ; Shuyi Zhang ; Jiayi Liu ; Wenlian Chen ; Lingshuang Liu ; Ling Xu ; Jiatuo Xu
Digital Chinese Medicine 2025;8(3):351-362
Objective:
To explore the feasibility of constructing a lung cancer early-warning risk model based on facial image features, providing novel insights into the early screening of lung cancer.
Methods:
This study included patients with pulmonary nodules diagnosed at the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 1, 2019 to December 31, 2024, as well as patients with lung cancer diagnosed in the Oncology Departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and Longhua Hospital during the same period. The facial image information of patients with pulmonary nodules and lung cancer was collected using the TFDA-1 tongue and facial diagnosis instrument, and the facial diagnosis features were extracted from it by deep learning technology. Statistical analysis was conducted on the objective facial diagnosis characteristics of the two groups of participants to explore the differences in their facial image characteristics, and the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables. Based on the screened feature variables, four machine learning methods: random forest, logistic regression, support vector machine (SVM), and gradient boosting decision tree (GBDT) were used to establish lung cancer classification models independently. Meanwhile, the model performance was evaluated by indicators such as sensitivity, specificity, F1 score, precision, accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), and the area under the precision-recall curve (AP).
Results:
A total of 1 275 patients with pulmonary nodules and 1 623 patients with lung cancer were included in this study. After propensity score matching (PSM) to adjust for gender and age, 535 patients were finally included in the pulmonary nodule group and the lung cancer group, respectively. There were significant differences in multiple color space metrics (such as R, G, B, V, L, a, b, Cr, H, Y, and Cb) and texture metrics [such as gray-levcl co-occurrence matrix (GLCM)-contrast (CON) and GLCM-inverse different moment (IDM)] between the two groups of individuals with pulmonary nodules and lung cancer (P < 0.05). To construct a classification model, LASSO regression was used to select 63 key features from the initial 136 facial features. Based on this feature set, the SVM model demonstrated the best performance after 10-fold stratified cross-validation. The model achieved an average AUC of
9.Correlation between depressive symptom and traditional Chinese medicine constitution among school aged children and adolescents
Chinese Journal of School Health 2025;46(9):1222-1225
Objective:
To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom.
Methods:
From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted.
Results:
The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05).
Conclusions
Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.
10.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.


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