1.Analysis of tear film stability and corneal nerve changes in patients with Parkinson's disease
Yujie* LI ; Cancan* SHI ; Haoyu ZHAI ; Xiaofan YU ; Xinke LI ; Ning MU ; Mingxin LI ; He WANG
International Eye Science 2025;25(2):206-212
AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.
2.0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in the treatment of moderate to severe dry eye associated with diabetes mellitus
Cancan SHI ; Xinshu LIU ; Shuwen CHEN ; Yingyi ZHAO ; Xiaofan YU ; He WANG ; Mingxin LI
International Eye Science 2025;25(6):886-893
AIM:To evaluate the clinical efficacy of 0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in treating patients with type 2 diabetes mellitus(T2DM)and moderate-to-severe dry eye.METHODS:A total of 120 T2DM patients(120 eyes)with moderate-to-severe dry eye, treated at the endocrinology and ophthalmology departments at the Affiliated Hospital of Xuzhou Medical University from January 2024 to September 2024, were enrolled in the study. The patients were randomly divided into two groups: combination group [0.05% cyclosporine eye drops(Ⅱ)+ sodium hyaluronate eye drops] and control group(sodium hyaluronate eye drops alone), with 60 cases(60 eyes)in each group. Assessments were conducted at baseline and at 1, 2, and 3 mo post-treatment, including the ocular surface disease index(OSDI), non-contact tear meniscus height(NITMH), first non-invasive tear breakup time(NIBUTf), meibomian gland loss score, lipid layer thickness grade, conjunctival hyperemia grade, and corneal fluorescein staining(FL)score. At 3 mo after treatment, changes in tear inflammatory factors were observed, and corneal subbasal nerve plexus(SBN)morphology/density were analyzed using in vivo confocal microscopy(IVCM).RESULTS:At 1, 2, and 3 mo post-treatment, both groups showed statistically significant increases in NITMH and NIBUTf compared to baseline(all P<0.05), with greater improvement observed in the combination group(both P<0.05). OSDI and FL scores significantly decreased from baseline(all P<0.05), with more pronounced reductions in the combination group(both P<0.05). Meibomian gland loss scores showed no significant improvement in either group(all P>0.05). At 3 mo after treatment, tear levels of interleukin 6(IL-6)and matrix metalloproteinase-9(MMP-9)significantly decreased in both groups(all P<0.001), with a greater reduction noted in the combination group(both P<0.001). The combination group displayed increased corneal nerve branch density and nerve fiber density, along with decreased nerve tortuosity and dendritic cell(DC)density compared to baseline(all P<0.001), while the control group did not show significant changes(all P>0.05).CONCLUSION: The combination of 0.05% cyclosporine eye drops(Ⅱ)and sodium hyaluronate eye drops significantly improves clinical outcomes in T2DM patients with moderate-to-severe dry eye. This treatment effectively alleviates ocular surface inflammation, restores corneal nerve morphology and density, and demonstrates a favorable safety profile.
3.Relationship between physical activity and sarcopenia among elderly people in ten provinces (autonomous regions) of China, 2022—2023
Yuchen WANG ; Huijun WANG ; Yuna HE ; Chang SU ; Jiguo ZHANG ; Wenwen DU ; Xiaofang JIA ; Feifei HUANG ; Li LI ; Jing BAI ; Yanli WEI ; Xiaofan ZHANG ; Fangxu GUAN ; Yifei OUYANG
Journal of Environmental and Occupational Medicine 2025;42(6):661-667
Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of
4.Mechanism of Pharmacological Liver and Kidney Injuries of Dictamni Cortex Based on UPLC-Q-TOF-MS
Jiahe YAN ; Sujie LIU ; Xiaofan WANG ; Chen WANG ; Jiaxin RUAN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):48-56
ObjectiveThis study aims to reveal the mechanism of liver and kidney injuries caused by Dictamni Cortex and its interrelationship by metabonomics analysis of liver and kidney via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). MethodsThe content of the marker compounds of Dictamni Cortex was measured by high-performance liquid chromatography (HPLC) to carry out quality control. Sprague Dawley (SD) rats were randomly divided into a blank group (normal saline), an administration group (0.9, 2.7, 8.1 g·kg-1), and a high-dose withdrawal control group, with eight rats in each group. Continuous administration was performed once daily for 28 days. The liver and kidney injuries caused by each administration group were assessed by organ indices, pathological observations, and serum and plasma biochemical indices measured by enzyme-linked immunosorbent assay (ELISA). The potential biomarkers of liver and kidney injuries caused by Dictamni Cortex were screened, and pathway enrichment analysis and correlation analysis were performed based on UPLC-Q-TOF-MS. ResultsCompared with the blank group, both the medium- and low-dose groups showed insignificant damage to the liver and kidney of rats. The high-dose group exhibited the most serious damage, and the level of liver and kidney function indices [alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), and blood urea nitrogen (BUN)] and serum inflammatory indices ([interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)] in the serum were significantly changed (P<0.01). The liver and kidney metabolism pathways and differential metabolites were quite different. Among them, phenylalanine metabolism, niacin and nicotinamide metabolism, and glycerophospholipid metabolism were common pathways. Correlation analysis of differential metabolites showed that there were significant correlations among disorders of 4′-Phosphopantothenoylcysteine, PC (16∶0/15∶0), phenylethylamine, arachidonic acid, and linoleic acid in liver and kidney tissue. ConclusionThe decoction of Dictamni Cortex can cause liver and kidney injuries, and its mechanism may be related to oxidative stress and lipid metabolism disorders. The correlation of differential metabolites indicates the interaction between liver and kidney injuries.
5.Metabolomics Reveals Immune System Domage of Dictamnine
Xiaocan GAI ; Jiaxin RUAN ; Sujie LIU ; Chen WANG ; Xiaofan WANG ; Jiahe YAN ; Yu WANG ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):57-65
ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine (DIC) in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank (normal saline), DIC (10 mg·kg-1), and DIC withdrawal (recovery period) groups (n=8). The rats were continuously treated for 7 days, once a day, and the body weight and organ weight were recorded. The levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) in the serum and immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to screen the potential biomarkers of immune inflammation caused by DIC, and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β, TNF-α, lysophosphatidylcholine acyltransferase 2 (LPCAT2), and farnesoid X receptor (FXR) in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, the DIC group showed elevated levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01), and the DIC withdrawal group showcased lowered levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01). The levels of IgA, IgG, and IgM in the spleen of rats in the DIC group were decreased (P<0.01), while those in the DIC withdrawal group were recovered (P<0.05, P<0.01). Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC (32∶0), LysoPC (20∶4/0∶0), LysoPC (P-18∶0/0∶0), taurochenodeoxycholic acid, taurocholic acid, LysoPC [20∶5(5Z,8Z,11Z,14Z,17Z)/0∶0], chenodeoxycholic acid, arachidonic acid, LysoPC (18∶0/0∶0), LysoPC (15∶0/0∶0), LysoPC (16∶0/0∶0), and LysoPC (17∶0/0∶0) as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC, lipid metabolism disorders such as glycerophospholipid metabolism, primary bile acid metabolism, and arachidonic acid metabolism were enriched, which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group, the DIC group exhibited up-regulated mRNA levels of IL-1β, TNF-α, LPCAT2, and FXR (P<0.01), and the up-regulation was decreased in the withdrawal group (P<0.01). ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites, regulate the inflammatory metabolic pathway, reduce the inflammation level, and alleviate the metabolic disorders, thus attenuating the potential toxicity induced by DIC.
6.An analysis of epidemiological characteristics of influenza-like illness in Hongkou District, Shanghai from 2015 to 2024
Zhenzhen QI ; Tong LI ; Xiaofan REN ; Haiyan WANG ; Jixing YANG
Shanghai Journal of Preventive Medicine 2025;37(8):649-653
ObjectiveTo explore the epidemic levels and epidemiological characteristics of influenza-like illness (ILI) in Hongkou District of Shanghai, to track the trends in virus mutations, so as to offer a scientific foundation for precisely predicting influenza epidemic trends, providing early alerts, and implementing prompt prevention and control measures. MethodsData on ILI and etiological surveillance from Hongkou District between 2015 and 2024 were collected and statistically analyzed. ResultsThe consultation percentage of ILI (ILI%) in Hongkou District from 2015 to 2024 was 0.58%, and the differences were statistically significant between different years (χ²=19 280.500, P<0.001), with winter and summer being the prevalence peaks. The highest proportion of ILI cases was observed in the 25‒<60 years age group, and the proportion of cases aged ≥60 years showed an increasing trend. The positive rate for influenza viruses was 17.60%, with seasonal influenzaA (H3N2) subtype (49.78%) and influenza A(H1N1) (30.03%) being the predominant strains,and the positive rate was different by years. There was a correlation between ILI% and the positive rate of influenza viruses (r=0.260, P<0.001). The median intensity of influenza activity in 2023‒2024 was 23.09, which was significantly higher than that in 2015‒2019 (H=37.052, P<0.001) and that in 2020‒2022 (H=40.436, P<0.001). ConclusionFrom 2015 to 2022, the ILI% in Hongkou District, Shanghai remained at a relatively low level, but it significantly increased in 2023‒2024, with peaks observed in winter and summer. The predominant influenza virus strains varied and alternated by years. The 2023‒2024 period witnessed an intensified influenza activity. It is necessary to continuously monitor the impact of other respiratory pathogens on influenza epidemic, so as to provide a scientific basis for early warning and prevention and control of influenza.
7.Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching
Jinxi YUE ; Linjun WAN ; Gang WANG ; Ruiling ZHANG ; Xiaoran ZHANG ; Ouya LIU ; Xiaofan YU ; Qingqing HUANG ; Zongfang REN
Chinese Critical Care Medicine 2024;36(1):73-77
Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.
8.Construction and preliminary application of a training program of operating room nurses for returning to work after delivery based on work adaptation theory
Ping BAI ; Yongting WEI ; Zhichao SUN ; Xiaofan DONG ; Jianhua WANG ; Feng WANG ; Qi YAO
Chinese Journal of Nursing 2024;59(1):77-84
Objective To construct a training program for retuming to work after delivery based on Morrison's job adaptation theory in operating room nurses and to explore its application effect.Methods On the basis of literature research and Delphi expert consultation method,a training program of postpartum return of operating room nurses was constructed.From August 2021 to December 2022,the preliminary application of this research program was carried out,with 6 cases in an experimental group and 5 cases in a control group.The differences between the 2 groups were compared by Job Adaptation Scale,Psychological Resilience Scale and satisfaction evaluation,and the application effect was evaluated.Results After 2 rounds of correspondence,a training program for postpartum return of operating room nurses was formed,which included 4 first-level indicators(role adaptation,task adaptation,environment adaptation and cultural adaptation),and 32 second-level indicators.The authority coefficients of the 2 rounds of correspondence consultation were 0.908 and 0.917,and the Kendall W coefficients were 0.224 and 0.206,respectively(both P<0.001).The preliminary application results showed that there were statistically significant differences in job adaptation and satisfaction evaluation between the 2 groups(both P<0.05).There was no significant difference in psychological resilience score between groups(P>0.05).Conclusion The postpartum retum training program for operating room nurses established in this study is scientific and practical to a certain extent.In the future,samples can be expanded and multi-center studies can be carried out to further test the practicability and effectiveness of the program.
9.Quantitative analysis of foot kinematics in patients with early Parkinson′s disease under dual task
Haohao WANG ; Xiaofan XUE ; Dongtao LIU ; Zhou LONG ; Cheng WANG ; Lichun ZHOU
Chinese Journal of Neurology 2024;57(3):255-265
Objective:To investigate the gait characteristics of patients with early Parkinson′s disease (PD) under cognitive dual task, and to provide sensitive kinematic indicators for the early diagnosis, timely treatment and reasonable rehabilitation of PD.Methods:A total of 62 outpatients and inpatients with early non-tremor Parkinson′s disease in Shijingshan Branch of Beijing Chaoyang Hospital Affiliated to Capital Medical University from September 2021 to August 2023 were selected as experimental group (PD group), and 62 healthy controls with comparable age composition ratio were selected as control group. The baseline data, Montreal Cognitive Assessment Scale scores, and the gait assessment scores of the motor part of the Unified Parkinson′s Disease Rating Scale were compared between the 2 groups. The wearable gait analysis device was used to collect the gait parameters of the 2 groups of subjects under single task and dual task, and the foot kinematic characteristics of the patients with early PD were quantified. Independent sample t test and Mann-Whitney U test were used to analyze the gait parameters of the 2 groups. The statistically significant variables were included in Logistic regression analysis to explore the association between gait parameters and PD. Finally, the diagnostic value of the variables was estimated by receiver operating characteristic (ROC) curve analysis. Results:Gait spatio-temporal parameters (per gait cycle): (1) The gait speed of the PD group was slower than that of the control group [(1.01±0.12) m/s vs (1.22±0.18) m/s, t=-7.526] during single task walking. The bipedal support time in the PD group was significantly longer than that in the control group [(0.29±0.05) s vs (0.22±0.06) s, t=6.659]. The differences were both statistically significant (both P<0.001). (2) During dual-task walking, PD patients showed slower gait speed [(0.88±0.11) m/s vs (1.19±0.16) m/s, t=-12.158, P<0.001]. The bipedal support time in the PD group was longer than that in the control group [(0.36±0.05) s vs (0.22±0.05) s, t=12.828, P<0.001]. PD patients had shorter stride length [(109.20±6.21) cm vs (112.77±5.87) cm, t=-3.203, P=0.010]. Stride frequency in the PD group was higher than that in the control group [(114.45±7.10) steps/min vs (110.87±7.16) steps/min, t=2.724, P=0.020]. The single leg support time was longer than that of the control group [(0.49±0.12) s vs (0.45±0.06) s, t=2.643, P=0.020] , and the differences were statistically significant. Gait kinematics parameters: (1) During single task walking, the maximum angle of foot movement in the sagittal plane in the PD group was smaller than that in the control group (17.19°±2.37° vs 19.71°±2.92°, t=-4.691, P<0.001). The minimum angle of movement in the sagittal plane was smaller than that in the control group (-67.08°±4.63° vs -70.10°±3.94°, t=0.395, P=0.001). The minimum horizontal angle of the foot during exercise in the PD group was lower than that in the control group (9.08°±4.02° vs 11.80°±3.60°, t=-3.461, P<0.001). The minimum angle of the foot coronal plane in the PD group was smaller than that in the control group (-10.55°±2.87° vs -12.04°±2.31°, t=2.831, P=0.030; the negative sign only represents the movement direction). The touch angle of the foot in the PD group was significantly lower than that in the control group (11.14°±2.78° vs 12.78°±3.57°, t=-2.779, P=0.030). (2) During dual-task walking, the maximum sagittal angle (15.44°±2.54° vs 18.99°±2.71°, t=-6.673, P<0.05), the minimum angle of sagittal plane (-65.68°±4.73° vs -70.02°±4.04°, t=-4.747, P<0.001; the negative sign only represents the direction of movement), the minimum coronal movement angle (-11.15°± 2.99° vs -13.18°±2.50°, t=3.642, P=0.020), the touch angle (11.01°±3.10° vs 12.83°±4.01°, t=-2.438, P=0.010), the minimum horizontal angle (8.83°±4.04° vs 11.83°±3.63°, t=-3.776, P<0.001), and the change of the angle from the ground (-65.00°±3.54° vs -67.06°±3.61°, t=3.133, P<0.001) in the PD group were all smaller than that in the control group. The differences were all statistically significant. Logistic regression analysis showed that step frequency was positively correlated with PD ( OR=1.124,95% CI 1.040-1.201, P=0.001), minimum angle of coronal plane was positively correlated with PD ( OR=1.501, 95% CI 1.040-2.151, P=0.030). Stride length was negatively correlated with PD ( OR=0.902, 95% CI 0.830-0.978, P=0.010). ROC curve was used to evaluate the diagnostic value of step frequency, stride length and minimum angle of coronal plane. For step frequency, when the maximum Youden index was 0.880, the best cut-off value to distinguish the PD group from the control group was 115.000, the sensitivity was 0.577, the specificity was 0.710, and the area under the curve was 0.656. For the minimum coronal angle, when the maximum Youden index was 0.251, the best cut-off value was -12.575, the sensitivity was 0.728, the specificity was 0.531, and the area under the curve was 0.670. For stride length, when the maximum Youden index was 0, the best cut-off value was 100.91, the sensitivity was 0.950, the specificity was 0.050, and the area under the curve was 0.300. Conclusions:Some gait parameters such as step frequency and minimum angle of coronal plane can be used as kinematic markers to reflect the gait characteristics of early PD, which may be helpful in tracking and evaluating the gait disorder characteristics of early PD patients and predicting the risk of PD. Some gait parameters of PD patients are significantly different from those of healthy people during cognitive-motor dual-task walking.
10.Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway
Jiaxin GAO ; Jianbo WANG ; Yanan XUE ; Jie SUN ; Dan WANG ; Kun HAN ; Yunyu ZHANG ; Yiran YIN ; Xiaofan FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):10-17
ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan(QWBZS) on diabetic encephalopathy(DE) rat model, and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β) signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group(8 rats) and high-fat diet group(40 rats). After 12 weeks of feeding, rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin(STZ) for 2 consecutive days to construct a DE model, and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling, according to blood glucose and body weight, model rats were randomly divided into model group, low, medium and high dose groups of QWBZS(3.15, 6.3, 12.6 g·kg-1), combined western medicine group(metformin+rosiglitazone, 0.21 g·kg-1), with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage, and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage, 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin (FINS) level was detected by enzyme-linked immunosorbent assay(ELISA) and insulin resistance index(HOMA-IR) was calculated. Hematoxylin-eosin(HE) staining was used to observe the morphological changes of hippocampus in rats, ELISA was used to detect the indexes of oxidative stress in hippocampal tissues, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect mRNA expression levels of PI3K, Akt, nuclear transcription factor-κB(NF-κB), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in hippocampus, and Western blot was used to detect the protein expression of PI3K, Akt, phosphorylated(p)-Akt, GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group, FINS and HOMA-IR values of the model group were significantly increased(P<0.01), the path of finding the original position of the platform was significantly increased, and the escape latency was significantly prolonged(P<0.01), the morphology of neuronal cells in hippocampal tissues was disrupted, the levels of reactive oxygen species(ROS) and malondialdehyde(MDA) in hippocampus of rats were increased, and the activity of superoxide dismutase(SOD) was decreased(P<0.05, P<0.01), mRNA expression levels of PI3K and Akt were decreased(P<0.01), mRNA expression levels of NF-κB, TNF-α and IL-1β were increased(P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly decreased, and the protein expression of GSK-3β was significantly increased(P<0.01). Compared with the model group, the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased(P<0.01), the path of finding the original position of the platform and the escape latency were significantly shortened(P<0.01), the hippocampal tissue structure of rats was gradually recovered, and the morphological damage of nerve cells was significantly improved, the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased(P<0.01), the mRNA expression levels of PI3K and Akt were increased(P<0.01), and the mRNA expression levels of NF-κB, TNF-α and IL-1β were decreased (P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly increased(P<0.01), and the expression of GSK-3β was significantly decreased(P<0.01). ConclusionQWBZS can alleviate insulin resistance in DE rats, it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

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