1.Clinical observation on rapid relief of dyspnea in juvenile-onset recurrent respiratory papillomatosis treated with bevacizumab
Yufei PAN ; Zhenkun YU ; Yuanyuan LU ; Huili HUANG ; Kai LIU ; Huiying HU ; Yonghui ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(1):52-57
Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.
2.Epidemiological investigation of PCV2 and distribution of swine farms in Henan province 2022-2023
Zhenkun LI ; Jin YUAN ; Hao LU ; Jinchao XING ; Yang LI ; Fangting DONG ; Menglong XU ; Yue ZHANG ; Zhanyong WEI
Chinese Journal of Veterinary Science 2025;45(5):926-933
This study aims to investigate the epidemic variation of porcine circovirus type2(PCV2)and its distribution in swine farms in Henan Province from 2022 to 2023.In this study,1 206 pig blood samples from 18 urban scale swine farms,and 318 pigs and environmental samples from 2 PCV2-positive swine farms in Henan Province were detected by fluorescence quantitative PCR.ORF2 gene sequencing and genetic evolution analysis were performed on the positive samples.The results showed that the positive rate of PCV2 was 7.05%(85/1 206)in Henan Province,11.15%in western Henan Province and 3.03%in southern Henan Province.The positive rate of PCV2 in spring was 11.60%(67/576).A total of 31 ORF2 gene sequences were obtained,of which 23 were PCV2d(74.19%),6 were PCV2a(19.35%),one was PCV2b(3.23%)and one was PCV2c(3.23%).The results of amino acid sequence comparison showed that the mutation sites mainly concentrated on amino acids at positions 40-68 and 180-209.The total positive rate of pig farm sam-ples was 37.42%(119/318),and the positive rate of pig samples from different types of pig houses was 60.71%(34/56),45.83%(11/24),35.09%(20/57),and 33.33(3/9)in order from high to low.The positive rate of environmental samples from high to low was 56.36%(31/55)in feeding system,46.67%(7/15)in feces system,12.50(1/8)in decontamination area,11.11%(2/18)in living area,and no PCV2 was detected in ventilation system.The highest positive rate was 45.00%(9/20)for the tools in the house,7.14%(1/14)for the surface and sole of the clothes after leaving the house,and no PCV2 was detected on the surface and sole of the clothes before entering the house.In this study,the epidemiological investigation of PCV2 in Henan Province and its distribu-tion in swine farms were carried out,and the main circulating strains,seasons,regions and gene mutations of PCV2 in H enan Province were identified.The distribution and transmission routes of PCV2 in positive pig farms were preliminarily analyzed and summarized,which provided data basis and reference for effective prevention and control of PCV and the establishment of accurate bio-safety prevention and control measures.
3.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
4.Epidemiological investigation of PCV2 and distribution of swine farms in Henan province 2022-2023
Zhenkun LI ; Jin YUAN ; Hao LU ; Jinchao XING ; Yang LI ; Fangting DONG ; Menglong XU ; Yue ZHANG ; Zhanyong WEI
Chinese Journal of Veterinary Science 2025;45(5):926-933
This study aims to investigate the epidemic variation of porcine circovirus type2(PCV2)and its distribution in swine farms in Henan Province from 2022 to 2023.In this study,1 206 pig blood samples from 18 urban scale swine farms,and 318 pigs and environmental samples from 2 PCV2-positive swine farms in Henan Province were detected by fluorescence quantitative PCR.ORF2 gene sequencing and genetic evolution analysis were performed on the positive samples.The results showed that the positive rate of PCV2 was 7.05%(85/1 206)in Henan Province,11.15%in western Henan Province and 3.03%in southern Henan Province.The positive rate of PCV2 in spring was 11.60%(67/576).A total of 31 ORF2 gene sequences were obtained,of which 23 were PCV2d(74.19%),6 were PCV2a(19.35%),one was PCV2b(3.23%)and one was PCV2c(3.23%).The results of amino acid sequence comparison showed that the mutation sites mainly concentrated on amino acids at positions 40-68 and 180-209.The total positive rate of pig farm sam-ples was 37.42%(119/318),and the positive rate of pig samples from different types of pig houses was 60.71%(34/56),45.83%(11/24),35.09%(20/57),and 33.33(3/9)in order from high to low.The positive rate of environmental samples from high to low was 56.36%(31/55)in feeding system,46.67%(7/15)in feces system,12.50(1/8)in decontamination area,11.11%(2/18)in living area,and no PCV2 was detected in ventilation system.The highest positive rate was 45.00%(9/20)for the tools in the house,7.14%(1/14)for the surface and sole of the clothes after leaving the house,and no PCV2 was detected on the surface and sole of the clothes before entering the house.In this study,the epidemiological investigation of PCV2 in Henan Province and its distribu-tion in swine farms were carried out,and the main circulating strains,seasons,regions and gene mutations of PCV2 in H enan Province were identified.The distribution and transmission routes of PCV2 in positive pig farms were preliminarily analyzed and summarized,which provided data basis and reference for effective prevention and control of PCV and the establishment of accurate bio-safety prevention and control measures.
5.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
6.Clinical observation on rapid relief of dyspnea in juvenile-onset recurrent respiratory papillomatosis treated with bevacizumab
Yufei PAN ; Zhenkun YU ; Yuanyuan LU ; Huili HUANG ; Kai LIU ; Huiying HU ; Yonghui ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(1):52-57
Objective:To evaluate the efficacy of bevacizumab in reducing dyspnea, avoiding tracheostomy, and assessing the overall safety and effectiveness of the treatment in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP).Methods:This study included 19 patients with JORRP treated with Bevacizumab at the Department of Otolaryngology-Head and Neck Surgery, BenQ Medical Center, from March 2022 to June 2024. The age of patients ranged from 1.0 to 27.0 years (10.47±8.45 years), with age at onset ranging from 0.5 to 15.0 years (3.66±3.70 years). The cohort included 11 males and 8 females. Bevacizumab was administered intravenously at a dose of 10 mg/kg every three weeks for three sessions. Efficacy was evaluated by comparing the standardized lesion volume pre-and post-treatment, with statistical analysis performed using R software (4.3.1).Results:Among the 19 patients, 11 presented with dyspnea before treatment. All patients experienced varying degrees of dyspnea relief within 72 hours following the initial treatment, and only one patient had mild dyspnea by the second treatment session three weeks later. The average reduction rates at 24 and 48 hours post-initia treatment were 25.75% and 47.16%, respectively. Following three treatment cycles, the average cumulative reduction rate was 67.47%, significantly higher than after the first treatment ( Z=3.38, P=0.002). Throughout the treatment period, no adverse events that of grade 2 or higher were noted. Conclusions:Bevacizumab can rapidly alleviate dyspnea symptoms and significantly reduce lesion volume in JORRP patients, exhibiting satisfactory overall safety and effectiveness. However additional large-scale prospective studies are warranted to validate its long-term safety and efficacy.
7.Effect of the different doses of remifentanil combined with dexmedetomide on the reduction in clam-ping reduction of cricoarytenoid joint dislocation
Lixiang YU ; Zhenkun YU ; Chuanzong YANG ; Yuanyuan LU ; Mengzhen ZHOU ; Chenhui JIANG ; Wen KONG ; Guangkui LU ; Li LU
The Journal of Clinical Anesthesiology 2024;40(10):1034-1038
Objective To compare the analgesic effect and the effect on the success rate of reduc-tion of three doses of remifentanil combined with dexmedetomidine in the clamping reduction of cricoarytenoid joint dislocation.Methods Fifty-one patients with cricoarytenoid joint dislocation,30 males and 21 females,aged 18-80 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were selected from April 2021 to December 2022 in the department of otolaryngology,head and neck surgery.The patients were randomly divided into three groups according to remifentanil dose:remifentanil 0.5 μg·kg-1·min-1 group(group A,n=17),remifentanil 1.0 μg·kg-1·min-1 group(group B,n=18),and remifentanil 1.5 μg·kg-1·min-1 group(group C,n=16).After admission,dexmedetomidine 0.6 μg·kg 1·h-1 was injected intravenously,and an ear,nose and throat anesthetic spray(2%lidocaine 2 ml)was used to administer surface anesthesia to the base of the tongue.A second surface anesthesia was administered to the throat at 5 minutes,and dexmedetomidine was stopped at 10 minutes.The supraglottic and periarticular cri-coarytenoid joints were subjected to superficial anesthesia for a third time under visual laryngoscope,and then remifentanil at corresponding doses was injected intravenously in three groups for 5 minutes,and the reduction operation began after the pumping was stopped.The success of the first reduction,the anesthesia quality satisfaction score of the surgeon and the recovery of remifentanil during the operation were recorded.VAS pain scores were recorded at the time of entry,3 minutes,30 minutes,and 6 hours after operation.The adverse reactions during operation and recovery were recorded.Results Compared with group B,the success rate of first reduction and the score of anesthesia quality satisfaction were significantly decreased in groups A and C(P<0.05).Compared with group A,the ratio of additional remifentanil supplementation in groups B and C was significantly reduced,and the VAS pain score 3 minutes after surgery was significant-ly decreased(P<0.05).Compared with group C,the proportion of mandibular manipulation ventilation in groups A and B was significantly reduced(P<0.05).There was no significant difference in the incidence of bradyheart rate,nausea and vomiting,agitation,delirium and laryngeal spasm between the three groups.Conclusion Compared with remifentanil 0.5 and 1.5 μg·kg-1·min-1,remifentanil 1.0 μg·kg-1·min-1 combined with dexmedetomide sequential pumping provided good analgesic effect for the clamping reduction of cricoarytenoid joint dislocation,improved the success rate of the first reduction,more stable respiratory circulation and fewer perioperative adverse reactions.
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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