1.Epidemiological investigation of a cluster of rural severe fever with thrombocytopenia syndrome cases and tick ecological monitoring results in Zibo City
Jun DU ; Ai-min FENG ; Bao-qiang CUI ; Tao SUN ; Yi-chuan YANG ; Yan-dong WANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):128-133
Objective To understand the epidemiological characteristics of a clustered outbreak of severe fever with thrombocytopenia syndrome(SFTS)as well as the ecological tick monitoring results for Zibo City, and to provide a scientific basis for formulating prevention and control strategies. Methods A case definition was cited before epidemic investigations were performed. Epidemiological investigations were performed on the index cases and their close contacts. Blood samples were collected from cases and close contacts, and quantitative real-time RT-PCR was used to detect SFTS virus(SFTSV)nucleic acid sequences. A retrospective cohort study was conducted to analyze risk factors and develop prevention and control strategies. Results This clustered outbreak involved two index cases and six close contacts with no deaths. Case A exhibited symptom onset on July 26. SFTS was confirmed on August 2. Case B exhibited symptom onset on August 1, and SFTS was confirmed on August 3. Patient B reported a recent history of tick bites. In both index cases, the incubation period for SFTS was inferred to be 7-12 days. The time interval from symptom onset to clinical diagnosis in the two cases ranged from 2-8 days, with an average period of 5 days. SFTSV nucleic acid test result were positive for both patients, whereas all six close contacts tested negative. All captured ticks tested negative for SFTSV using quantitative real-time RT-PCR. The densities of parasitic and free-living ticks in the emergency monitoring area around the cases were 12.60 and 4.65 ticks/(flag·100 m). In 2024, the average parasitic tick index and free-living tick density index were 4.21 and 2.43 ticks/(flag ·100 m)in Yiyuan County, respectively. Conclusions No evidence of human-to-human transmission was found in the assessed SFTS clusters. The infections were likely acquired through tick bites during fieldwork, and the risk of a subsequent outbreak spreading was low.
2.Research Progress on Mechanism of NAD+ Metabolic Remodeling in Occurrence and Development of Glioblastoma Multiforme
Jiajia CHE ; Jinyuan DU ; Junhao BAO ; Xiting PAN ; Chengwen WANG ; Chuan XU ; Ying SHI
Cancer Research on Prevention and Treatment 2025;52(10):861-868
Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD+) metabolic remodeling playing a pivotal role. Dysregulation of NAD+ and its associated metabolic pathways sustains increased intracellular NAD+ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD+ metabolic remodeling in GBM, elucidates the mechanisms by which NAD+ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD+-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.
3.Epidemiological characteristics of Mycoplasma pneumoniae infection among hospitalized children with respiratory tract infections at Children's Hospital of Hebei Province,2016-2024
Hong-Fei DU ; Meng-Chuan ZHAO ; Xiao-Shuang ZHANG ; Shan-Shan ZHOU ; Jing HUANG ; Xin-Guang LIU ; Le WANG
Medical Journal of Chinese People's Liberation Army 2025;50(9):1097-1102
Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.
4.Multi-gene molecular identification and pathogenicity analysis of pathogens causing root rot of Atractylodes lancea in Hubei province.
Tie-Lin WANG ; Yang XU ; Xiu-Fu WAN ; Zhao-Geng LYU ; Bin-Bin YAN ; Yong-Xi DU ; Chuan-Zhi KANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(7):1721-1726
To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology*
;
Atractylodes/microbiology*
;
Phylogeny
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Plant Roots/microbiology*
;
Fusarium/classification*
;
China
;
Virulence
;
Fungal Proteins/genetics*
5.Buyang Huanwu Decoction targets PPARG/SPP1/CD44 signaling pathway: mechanisms of lipid dysregulation and treatment in idiopathic pulmonary fibrosis.
Gang-Gang LI ; Xiao-Chuan PAN ; Fei WANG ; Quan-Yu DU
China Journal of Chinese Materia Medica 2025;50(14):3821-3834
Idiopathic pulmonary fibrosis(IPF) is a chronic progressive interstitial lung disease characterized by a complex pathogenesis and limited treatment options. Although studies have indicated that lipid metabolism dysregulation is associated with the progression of IPF, the core regulatory mechanisms remain unclear. By integrating RNA sequencing data from the GEO database, we identified four key genes related to lipid metabolism: peroxisome proliferator-activated receptor gamma(PPARG), secreted phosphoprotein 1(SPP1), caspase 3(CASP3), and platelet endothelial cell adhesion molecule 1(PECAM1). Further validation using single-cell RNA sequencing revealed the cell-specific expression patterns of these genes. The results found that PPARG was significantly downregulated in alveolar macrophages while SPP1 was significantly upregulated. Mechanistic studies indicated that PPARG negatively regulated SPP1 expression, and the interaction between SPP1 and cluster of differentiation 44(CD44) activated intercellular signaling pathways that promoted fibrosis. Through network pharmacology and molecular docking, it was predicted that the bioactive components of the traditional Chinese medicine formula, namely Buyang Huanwu Decoction may target PPARG to modulate lipid metabolism pathways. In a bleomycin-induced rat model with IPF, this paper randomly divided the rats into six groups(control, group, model group, pirfenidone group, and low, middle, and high-dose groups of Buyang Huanwu Decoction). The results demonstrated that Buyang Huanwu Decoction treatment significantly improved tissue pathological damage, reduced collagen deposition, and alleviated lipid metabolism dysregulation. Western blot analysis confirmed that Buyang Huanwu Decoction mediated the upregulation of PPARG and inhibited the activation of the SPP1/CD44 pathway. The multi-omics study elucidated the role of the PPARG/SPP1/CD44 pathway as a key regulatory factor in lipid metabolism in IPF, providing evidence that Buyang Huanwu Decoction exerted its antifibrotic effects through this novel mechanism and thus offering new insights into the therapeutic prospects for IPF.
Animals
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Drugs, Chinese Herbal/administration & dosage*
;
Signal Transduction/drug effects*
;
PPAR gamma/genetics*
;
Humans
;
Osteopontin/genetics*
;
Lipid Metabolism/drug effects*
;
Idiopathic Pulmonary Fibrosis/genetics*
;
Hyaluronan Receptors/genetics*
;
Rats
;
Male
;
Rats, Sprague-Dawley
;
Molecular Docking Simulation
6.Research progress in oncolytic virus and immunotherapy for liver cancer
Chenyang DU ; Hongyan XU ; Jie ZHANG ; Chuan QIN ; Junhe ZHANG
Journal of Xinxiang Medical College 2024;41(2):187-190
Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.
7.Value of modified ROX index in predicting the prognosis of acute respiratory distress syndrome treated with high-flow nasal cannula oxygen therapy
Caixia ZHANG ; Xinwei WANG ; Xinnian LIU ; Chuan DU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(3):392-398
Objective:To evaluate the value of the ROX index [blood oxygen saturation (SpO 2)/fraction of inspiration O 2 (FiO 2)/respiratory rate (RR)], ROX-heart rate (HR) index (ROX index/HR × 100), modified ROX (mROX) index [partial pressure of oxygen in the blood (PaO 2)/FiO 2/RR], and mROX-HR index (mROX index/HR × 100) in predicting prognosis for patients with acute respiratory distress syndrome (ARDS) treated with high-flow nasal cannula oxygen therapy (HFNC). Methods:The clinical data of 100 patients with ARDS who received HFNC between January 2018 and December 2022 at The Third People's Hospital of Hubei Province, Jianghan University, were retrospectively analyzed. These patients were divided into two groups based on whether HFNC treatment was successful or not: a success group with 65 patients and a failure group with 35 patients. The differences in the ROX index, ROX-HR index, mROX index, and mROX-HR index in the observation group were observed at the designated time points: 2, 12, and 24 hours after HFNC treatment. Receiver operating characteristic (ROC) curves were utilized to evaluate the value of ROX index, ROX-HR index, mROX index, and mROX-HR index in predicting the success or failure of HFNC treatment at 2, 12, and 24 hours. Cutoff values were determined.Results:There were no significant differences in age, gender, body mass index, Acute Physiology and Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Assessment score, or the proportions of underlying diseases and pulmonary causes between the success and failure groups (all P > 0.05). Furthermore, there were no significant differences in baseline HR, RR, FiO 2, SpO 2, partial pressure of carbon dioxide (PaCO 2), PaO 2, pH, lactate, oxygenation index, ROX index, mROX index, ROX-HR index, or mROX-HR index between the two groups (all P > 0.05). The ROX index in the success group at 2, 12, and 24 hours after HFNC treatment was 6.86 ± 1.09, 6.31 ± 1.61, and 8.24 ± 2.29, respectively. These values were significantly higher than those in the failure group (6.36 ± 0.67, 5.65 ± 1.44, and 5.41 ± 0.84) at the corresponding time points ( F = 5.97, 4.04, 49.40, all P < 0.05). At 2, 12, and 24 hours after HFNC treatment, the mROX index in the success group was 5.94 ± 1.28, 5.74 ± 1.23, and 8.51 ± 2.64, respectively. These values were significantly higher than those in the failure group (5.26 ± 0.74, 4.80 ± 0.97, 4.81 ± 1.17) at the corresponding time points ( F = 8.23, 15.38, 61.79, all P < 0.05). At 2, 12, and 24 hours after HFNC treatment, the ROX-HR index in the success group was 6.53 ± 1.32, 6.85 ± 1.44, and 7.57 ± 1.47, respectively. These values were significantly higher than those in the failure group (5.79 ± 1.04, 5.87 ± 1.03, 5.57 ± 0.63) at the corresponding time points ( F = 8.28, 12.61, 58.34, all P < 0.05). At 2, 12, and 24 hours after HFNC treatment, the mROX-HR index in the success group was 6.11 ± 1.30, 6.86 ± 1.13, and 7.79 ± 1.79, respectively. These values were significantly higher than those in the failure group (5.20 ± 1.06, 5.66 ± 1.46, 4.92 ± 0.90) at the corresponding time points ( F = 12.60, 20.87, 78.56, all P < 0.05). The receiver operating characteristic curve analysis revealed that the optimal thresholds were 6.56, 6.02, 6.24, and 5.25 for the ROX index, mROX index, ROX-HR index, and mROX-HR index, respectively. The area under the curve (AUC) values were 0.63, 0.66, 0.68, and 0.72, with sensitivity of 55.4%, 47.7%, 56.9%, and 76.9%, and specificity of 71.4%, 91.4%, 77.1%, and 62.9%, respectively. At 12 hours after treatment, the optimal thresholds were 6.09, 5.53, 6.52, and 5.99, with AUC values of 0.62, 0.70, 0.67, and 0.80, sensitivity of 55.4%, 53.8%, 61.5%, and 80.0%, and specificity of 74.3%, 77.1%, 71.4%, and 74.3%, respectively. At 24 hours after treatment, the optimal thresholds were 6.23, 6.4, 5.99, and 6.22, with AUC values of 0.88, 0.90, 0.91, and 0.93, sensitivity of 81.5%, 80.0%, 87.7%, and 83.1%, and specificity of 91.4%, 94.3%, 80.0%, and 91.4%, respectively. Conclusion:The use of the ROX index, mROX index, ROX-HR index, and mROX-HR index can aid in predicting the prognosis of ARDS patients. The predictive value of these indices increases as treatment time progresses. The mROX-HR index offers marked advantages during the initial stages of treatment and could serve as a reliable early predictor.
8.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
9.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
10.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.


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