1.The systemic inflammatory response index as a risk factor for all-cause and cardiovascular mortality among individuals with coronary artery disease: evidence from the cohort study of NHANES 1999-2018.
Dao-Shen LIU ; Dan LIU ; Hai-Xu SONG ; Jing LI ; Miao-Han QIU ; Chao-Qun MA ; Xue-Fei MU ; Shang-Xun ZHOU ; Yi-Xuan DUAN ; Yu-Ying LI ; Yi LI ; Ya-Ling HAN
Journal of Geriatric Cardiology 2025;22(7):668-677
BACKGROUND:
The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States.
METHODS:
A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed.
RESULTS:
During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms.
CONCLUSIONS
SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.
2.Development of Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai
Huijiang SONG ; Haisheng MOU ; Qianru WANG ; Wanxin WANG ; Wei XUN ; Liping YANG ; Fulai SHEN
Chinese Journal of General Practitioners 2025;24(9):1114-1121
Objective:To formulate the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Methods:This was a qualitative study. This study was divided into 2 stages. The first stage of the study was conducted from June to August 2023 and involved the heads of the General Affairs Departments of the 47 community health service centers in Pudong New Area. These individuals completed online questionnaires to compile a database on the current status of matching supply and demand resources in community health service centers in Pudong New Area. The second stage of the study run from September 2023 to August 2024. Firstly, the functional modules of China′s community health service centers would be clarified through a literature review. The construction scale and design requirements of similar institutions at home and abroad would be benchmarked, as well as practical experience. The results of Phase 1 research would then be combined to form the " Community Health Service Center Infrastructure Configuration Requirements and Design Suggestions (Draft)". Then, relevant experts were brought together to discuss the draft and form the " Community Health Service Center Infrastructure Configuration Requirements and Design Recommendations (Revised Version)". The experts involved in the discussion specialized in the study of infrastructure resource allocation for medical institutions. Finally, the medical and healthcare system managers, community health service center users, and relevant commissions and bureaus of Pudong New Area were consulted to further revise and finalize the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Results:The total floor area of community health service centers in Pudong New Area was 57% (31/55), the number of beds per 1 000 people was 14% (8/55), and the total number of beds was 10% (6/60). These figures showed that urgent upgrades and construction in accordance with the new standards were required. The final " Guidelines for the Construction of Community Health Service Centers" of Shanghai Pudong New Area comprised 15 chapters, covering topics from the macro construction scale, site selection and general plan to architectural design, structural design, water supply and sewage treatment, ventilation and air conditioning, electrical systems, informatics, medical gas supply, indoor design, signage, marking and fire protection, etc. The guidelines have been revised to incorporate the functional design of the 5 basic rooms, with a particular focus on the creating humanistic spaces and promoting digitalization. Particular attention was paid to creating humanistic spaces and improving ageing with digital applications. Conclusions:The Guidelines for the Construction of Community Health Service Centers in Pudong New Area of Shanghai have been successfully formulated. These guidelines can be used to guide the subsequent high-quality and standardized development of community health service centers.
3.Analysis on current status and outcomes of comprehensive control of cardiovascular disease risk factors based on community population cohort
Caixia SU ; Xiaofei LIU ; Peng SHEN ; Yexiang SUN ; Tianjing ZHOU ; Ting WANG ; Qi CHEN ; Hongbo LIN ; Xun TANG ; Pei GAO
Chinese Journal of Epidemiology 2025;46(5):768-775
Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.
4.Relationship between long non-coding RNA and osteoarthritis
Shanbin ZHENG ; Tianwei XIA ; Jiahao SUN ; Zhiyuan CHEN ; Xun CAO ; Chao ZHANG ; Jirong SHEN
Chinese Journal of Tissue Engineering Research 2025;29(11):2357-2367
BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.
5.Distritution Characteristics of TCM Syndromes and Evaluation of Traditional Chinese Medicine Efficacy in 2506 Rheumatoid Arthritis Patients with Different Course of Disease:A Real-World Retrospective Study
Zhengyao SHEN ; Jingtao LI ; Yuchen YANG ; Shujuan ZHANG ; Quan JIANG ; Xun GONG
Journal of Traditional Chinese Medicine 2025;66(23):2453-2459
ObjectiveTo investigate the syndrome evolution patterns, characteristics of the used herbal medicinals, and efficacy variations across different stages of rheumatoid arthritis (RA) progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN), 2,506 RA patients were retrospectively enrolled and categorized into <6 months group (166 cases), 6 months to <5 years group (1063 cases), 5 to <20 years group (1067 cases), and ≥20 years group (210 cases). Syndromes were differentiated before and after traditional Chinese medicine (TCM) treatment, including damp-heat obstruction, wind-damp obstruction, cold-damp obstruction, blood stasis obstructed in the collaterals, phlegm-stasis obstruction, liver-kidney insufficiency, qi and blood deficiency, and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and 28-joint disease activity score based on C-reactive protein (DAS28-CRP) before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome (49/166, 29.5%), wind-dampness obstruction syndrome (46/166, 27.7%), and dampness-heat obstruction syndrome (43/166, 25.9%). For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years, the dominant syndrome was dampness-heat obstruction syndrome (324/1063, 30.5% and 318/1067, 29.8%, respectively). In patients with disease duration ≥20 years, liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated, each accounting for 25.24% (53/210). The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction (201/738, 27.2%), liver-kidney insufficiency (119/367, 32.4%), and phlegm-stasis obstruction syndromes (73/172, 42.4%). These were classified as high-frequency syndromes. After treatment, damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome, while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao (Radix et Rhizoma Glycyrrhizae) and Baishao (Radix Paeoniae Alba). In the <6 months group and the 6 months to <5 years group, high-frequency herbs also included Fangfeng (Radix Saposhnikoviae), Duhuo (Radix Angelicae Pubescentis), Chuanxiong (Rhizoma Chuanxiong), and Qianghuo (Radix et Rhizoma Notopterygii). In the 5 to <20 years group and the ≥20 years group, the usage of Huangqi (Radix Astragali), Fuling (Poria), Niuxi (Radix Achyranthis Bidentatae), and Danggui (Radix Angelicae Sinensis) increased, while the proportion of Fangfeng and Duhuo decreased. After treatment, the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased (P<0.05). There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups (P<0.01). Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group (OR=0.4), 5~20 years group (OR=0.5), and ≥20 years group (OR=0.4) compared to the <6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency, with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA, with superior efficacy in patients with disease duration shorter than 6 months.
6.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
Objective :
To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis.
Methods :
An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression.
Results :
Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01).
Conclusion
Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.
7.Analysis of iodine nutritional status monitoring results of children aged 8 - 10 and pregnant women in Xining City, Qinghai Province
Xun CHEN ; Mingjun WANG ; Hongting SHEN ; Jinmei ZHANG ; Yanan LI ; Peichun GAN ; Lansheng HU ; Shenghua CAI ; Hong JIANG ; Peizhen YANG ; Jing MA ; Huizhen YU ; Xianya MENG
Chinese Journal of Endemiology 2025;44(2):124-127
Objective:To investigate the iodine nutrition status of children aged 8 - 10 and pregnant women in Xining City, Qinghai Province.Methods:From 2019 to 2021, a stratified cluster sampling method was used to divide 7 counties (districts) under the jurisdiction of Xining City, Qinghai Province into 5 sampling areas according to east, west, south, north, and center each year. One township (town, street) was selected from each area. Forty non boarding students aged 8 to 10 from each primary school (half male and half female, age balanced) and 20 pregnant women from each township (town, street) location were selected to collect edible salt samples at home and a random urine sample to measure salt iodine and urinary iodine level. B-ultrasound was used to measure thyroid volume in children and the goiter rate was calculated.Results:A total of 6 534 samples of household edible salt were collected from children and pregnant women, with an average salt iodine concentration of 25.58 mg/kg. The coverage rate of iodized salt was 97.50% (6 371/6 534), and the qualified iodized salt consumption rate was 89.46% (5 845/6 534). A total of 4 362 urine samples were collected from children, with a median urinary iodine level of 183.10 μg/L. The difference between different years was statistically significant ( H = 20.27, P < 0.001). A total of 2 169 urine samples were collected from pregnant women, with a median urinary iodine level of 168.90 μg/L. The difference between different years was statistically significant ( H = 107.09, P < 0.001). A total of 3 336 cases of thyroid gland examination were conducted in children, including 33 cases of thyroid enlargement, with a goiter rate of 0.99%. There was a statistically significant difference between different years (χ 2 = 15.00, P < 0.001). Conclusion:From 2019 to 2021, children aged 8 to 10 and pregnant women in Xining City are at an appropriate level of iodine, and the achievements in prevention and treatment of iodine deficiency disorders still need to be continuously consolidated.
8.Association of triglyceride-glucose index and cardiovascular disease in a community-based Chinese cohort
Mengxi LU ; Qiuping LIU ; Tianjing ZHOU ; Xiaofei LIU ; Yexiang SUN ; Peng SHEN ; Hongbo LIN ; Xun TANG ; Pei GAO
Journal of Peking University(Health Sciences) 2025;57(3):430-435
Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95%confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8%of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34%)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P<0.001).The risk in the highest TyG quartile(TyG>9.10)was 42%higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95%CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P<0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P<0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.
9.Effect of electroacupuncture on hippocampal glycolysis via the regulation of the Akt/mTOR/HIF-1α signaling pathway in Alzheimer's disease model mice
Zhaoxie YU ; Yao WANG ; Yanan LI ; Chunfeng LYU ; Junling LI ; Xun ZHANG ; Zhipeng FENG ; Feng SHEN ; Yanchun WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1460-1469
Objective This study aimed to investigate the regulatory effect of electroacupuncture(EA)intervention on the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)signaling pathway in the hippocampal tissue of Alzheimer's disease(AD)model mice and its effect on astrocytic glycolytic function,further exploring how EA ameliorates AD-related cognitive impairment.Methods Eighteen APP/PS1 mice were randomly divided into model,EA,and sham EA groups(n=6)using the random number table method.Six wild-type C57BL/6J mice served as the control group.The EA group received EA stimulation at acupoints"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)(administered every other day,20 min per session,for 4 weeks).The sham EA group received identical needle insertions at the same acupoints without electrical stimulation.The control and model groups were only restrained.Cognitive function was assessed using the Morris water maze and Y-maze spontaneous alternation tests.Hippocampal morphology was observed via hematoxylin and eosin staining.Hippocampal β-amyloid peptide 1-42(Aβ1-42)deposition was detected using immunohistochemistry.HIF-1α protein expression,the p-Akt/Akt,and p-mTOR/mTOR ratios were measured using Western blotting.Pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)activities were quantified using enzyme-linked immunosorbent assay.Hexokinase(HK)activity and L-lactate content were determined using a colorimetric assay.Co-localization of LDHA with the astrocyte marker glial fibrillary acidic protein was quantitatively analyzed using immunofluorescence double-labeling combined with Pearson's correlation coefficient.Results Compared with the control group,the model group mice exhibited cognitive decline,as shown by prolonged escape latency(P<0.01),reduced number of platform crossings,lower time spent in the target quadrant,and decreased spontaneous alternation accuracy(P<0.01).The hippocampal neurons showed cell body swelling,deeper nuclear staining,enlarged intercellular spaces,and increased average optical density of Aβ1-42(P<0.01).The p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,were elevated(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels were significantly increased(P<0.01),and the co-localization coefficient of LDHA with astrocytes was enhanced.Compared to the model group,the EA group of mice showed improved cognitive function.The hippocampal neurons had more intact structures,with a more uniform cell distribution.The average optical density of Aβ1-42 decreased(P<0.01),and the p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,decreased(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels decreased(P<0.05),and the co-localization coefficient of LDHA with astrocytes significantly decreased(P<0.01).No significant improvement was observed in any of the indicators in the sham EA group compared with the EA group.Conclusion EA at"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)ameliorates cognitive dysfunction in AD model mice.The underlying mechanism may involve suppressing the overactivation of the hippocampal Akt/mTOR/HIF-1α signaling pathway,thereby downregulating key glycolytic enzyme activities and reducing abnormal lactate accumulation.Furthermore,the astrocytic glycolytic metabolic pathway may constitute a key therapeutic target for this intervention.
10.Effect of electroacupuncture on hippocampal glycolysis via the regulation of the Akt/mTOR/HIF-1α signaling pathway in Alzheimer's disease model mice
Zhaoxie YU ; Yao WANG ; Yanan LI ; Chunfeng LYU ; Junling LI ; Xun ZHANG ; Zhipeng FENG ; Feng SHEN ; Yanchun WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1460-1469
Objective This study aimed to investigate the regulatory effect of electroacupuncture(EA)intervention on the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)signaling pathway in the hippocampal tissue of Alzheimer's disease(AD)model mice and its effect on astrocytic glycolytic function,further exploring how EA ameliorates AD-related cognitive impairment.Methods Eighteen APP/PS1 mice were randomly divided into model,EA,and sham EA groups(n=6)using the random number table method.Six wild-type C57BL/6J mice served as the control group.The EA group received EA stimulation at acupoints"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)(administered every other day,20 min per session,for 4 weeks).The sham EA group received identical needle insertions at the same acupoints without electrical stimulation.The control and model groups were only restrained.Cognitive function was assessed using the Morris water maze and Y-maze spontaneous alternation tests.Hippocampal morphology was observed via hematoxylin and eosin staining.Hippocampal β-amyloid peptide 1-42(Aβ1-42)deposition was detected using immunohistochemistry.HIF-1α protein expression,the p-Akt/Akt,and p-mTOR/mTOR ratios were measured using Western blotting.Pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)activities were quantified using enzyme-linked immunosorbent assay.Hexokinase(HK)activity and L-lactate content were determined using a colorimetric assay.Co-localization of LDHA with the astrocyte marker glial fibrillary acidic protein was quantitatively analyzed using immunofluorescence double-labeling combined with Pearson's correlation coefficient.Results Compared with the control group,the model group mice exhibited cognitive decline,as shown by prolonged escape latency(P<0.01),reduced number of platform crossings,lower time spent in the target quadrant,and decreased spontaneous alternation accuracy(P<0.01).The hippocampal neurons showed cell body swelling,deeper nuclear staining,enlarged intercellular spaces,and increased average optical density of Aβ1-42(P<0.01).The p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,were elevated(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels were significantly increased(P<0.01),and the co-localization coefficient of LDHA with astrocytes was enhanced.Compared to the model group,the EA group of mice showed improved cognitive function.The hippocampal neurons had more intact structures,with a more uniform cell distribution.The average optical density of Aβ1-42 decreased(P<0.01),and the p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,decreased(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels decreased(P<0.05),and the co-localization coefficient of LDHA with astrocytes significantly decreased(P<0.01).No significant improvement was observed in any of the indicators in the sham EA group compared with the EA group.Conclusion EA at"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)ameliorates cognitive dysfunction in AD model mice.The underlying mechanism may involve suppressing the overactivation of the hippocampal Akt/mTOR/HIF-1α signaling pathway,thereby downregulating key glycolytic enzyme activities and reducing abnormal lactate accumulation.Furthermore,the astrocytic glycolytic metabolic pathway may constitute a key therapeutic target for this intervention.


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