1.Genome wide association study on genetic risk factors of deep vein thrombosis after trauma
Wenjie ZHANG ; Yu SU ; Shan LU ; Yuying CHEN ; Xiangyu CAO ; Lei LIU ; Li YANG ; Jun WU
Chinese Journal of Clinical Laboratory Science 2024;42(2):126-131
		                        		
		                        			
		                        			Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.
		                        		
		                        		
		                        		
		                        	
2.Iodine nutrition status of key population in Fuzhou City in 2021
Jinglan LIAO ; Xiangyu CAO ; Youqiong XU ; Lu LU ; Xiaoyang ZHANG
Chinese Journal of Endemiology 2024;43(1):56-60
		                        		
		                        			
		                        			Objective:To investigate the iodine nutrition status of key population in Fuzhou City, and to provide scientific basis for adjusting intervention strategies.Methods:From March to October 2021, a survey was conducted on iodine nutrition status of key population in 12 counties (cities, districts) of Fuzhou City. Each county (city, district) was divided into 5 sampling areas according to the east, west, south, north and middle directions. One township (street) was selected from each area, and 40 non-boarding children aged 8 - 10 (age balanced, half male and half female) from one primary school and 20 pregnant women (early, middle and late pregnancy balanced) were selected as survey subjects. Household salt samples and random urine samples were collected, and the salt iodine and urine iodine levels were tested by direct titration and arsenic and cerium catalytic spectrophotometry, respectively. Children's thyroid volume was measured by B-ultrasonography. At the same time, in cooperation with Fuzhou Maternal and Child Health Hospital, the thyroid stimulating hormone (TSH) testing results of heel blood of full-term natural delivery newborns in Fuzhou City in 2021 were collected.Results:A total of 2 400 children were monitored for salt iodine, urine iodine and goiter. The median salt iodine was 24.40 mg/kg, with an iodine salt coverage rate of 93.04% (2 233/2 400), a qualified rate of iodized salt of 97.40% (2 175/2 233), and a consumption rate of qualified iodized salt of 90.62% (2 175/2 400). The median urine iodine was 181.47 μg/L. The rate of goiter was 1.04% (25/2 400). A total of 1 200 pregnant women were monitored for salt iodine and urine iodine. The median salt iodine was 24.10 mg/kg, the coverage rate of iodized salt was 91.08% (1 093/1 200), the qualified rate of iodized salt was 97.90% (1 070/1 093), and the consumption rate of qualified iodized salt was 89.17% (1 070/1 200). The median urine iodine was 128.10 μg/L. The median TSH level in the heel blood of 14 242 newborns was 3.38 mU/L, and the proportion of TSH level > 5 mU/L was 30.96% (4 410/14 242).Conclusions:In 2021, children in Fuzhou City are at an appropriate level of iodine, but pregnant women are insufficient of iodine. We should continue to maintain comprehensive prevention and control measures mainly based on salt iodization, provide health education for pregnant women, and strengthen monitoring of TSH level in newborns.
		                        		
		                        		
		                        		
		                        	
3.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.
		                        		
		                        		
		                        		
		                        	
4.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.
		                        		
		                        		
		                        		
		                        	
5.A bibliometric analysis of nanoparticles in the treatment of non-small cell lung cancer
Xiangyu XU ; Lei YUAN ; Fei SUN ; Zhiming SHEN ; Yibo SHAN ; Yi LU ; Jianwei ZHU ; Wenxuan CHEN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1139-1147
		                        		
		                        			
		                        			Objective  To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.
		                        		
		                        		
		                        		
		                        	
6.Excess mortality risk associated with atmospheric PM2.5 exposure
ZHANG Kaiyue ; LI Xiaoqin ; XIA Junpeng ; DAI Xiangyu ; WU Jingjing ; JIANG Meng ; WANG Fang ; LU Shenghua
Journal of Preventive Medicine 2024;36(11):950-952,957
		                        		
		                        			Objective:
		                        			To evaluate the risk of fine particulate matter (PM2.5) on excess mortality among residents.
		                        		
		                        			Methods:
		                        			The data of residential mortality in Yangzhou City, Jiangsu Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The average daily mass concentration of PM2.5 and meteorology data were collected from the Yangzhou Environmental Monitoring Station and Yangzhou Meteorological Bureau, respectively. The effects of PM2.5 on non-accidental mortality, morality of respiratory diseases and mortality of circulatory diseases were evaluated using a generalized additive model. The risk of excess mortality was evaluated using excess risk (ER) and the number of excess mortality.
		                        		
		                        			Results:
		                        			The median average annual mass concentration of PM2.5 was 38.00 (interquartile range, 31.95) µg/m3 in Yangzhou City from 2015 to 2021, decreasing from 51.75 (interquartile range, 32.82) µg/m3 in 2015 to 28.00 (interquartile range, 23.42) µg/m3 in 2021. The median average annual number of non-accidental mortality, mortality of respiratory diseases and mortality of circulatory diseases were 96 (interquartile range, 22), 9 (interquartile range, 5) and 38 (interquartile range, 13) cases, respectively. The greatest effects of per 10 μg/m3 increase in PM2.5 mass concentration on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases were seen at a cumulative lag of 1 day (ER=0.528%, 95%CI: 0.293%-0.763%), a cumulative lag of 2 days (ER=0.917%, 95%CI: 0.125%-1.714%) and a cumulative lag of 1 day (ER=0.595%, 95%CI: 0.232%-0.961%), respectively. The number of excess mortality caused by PM2.5 on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases in Yangzhou City from 2015 to 2021 were 2 125, 412 and 977 cases, respectively; compared with 2015, the number of excess mortality in 2021 decreased by 66.95%, 75.53% and 64.42%, respectively.
		                        		
		                        			Conclusions
		                        			An increase in the mass concentration of atmospheric PM2.5 may elevate the risk of excess mortality among residents. Compared to 2015, the number of excess deaths attributed to exposure to atmospheric PM2.5 declined in 2021.
		                        		
		                        		
		                        		
		                        	
7.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.
		                        		
		                        		
		                        		
		                        	
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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