1.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
2.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
3.Analysis of the current status and influencing factors of attitudes and competence in hospice care among nursing interns
Shipeng SUN ; Yan JIA ; Wei ZHAO ; Rong WANG ; Xin GAO
Chinese Medical Ethics 2026;39(5):663-668
ObjectiveTo investigate the attitudes and competence of nursing interns toward hospice care, analyze the key factors influencing their performance, and provide targeted improvement suggestions to enhance their comprehensive quality. MethodsA total of 273 undergraduate nursing interns were investigated. General demographic data were collected, and the Chinese version of the Frommelt Attitude Toward Care of the Dying Scale, Form B (FATCOD-B) and the Hospice Care Competency Assessment Questionnaire were administered to evaluate their attitudes and competence in hospice care. A total of 270 valid questionnaires were recovered. Multiple linear regression was performed to analyze the influencing factors of hospice care attitudes and competence among nursing interns. ResultsThe total score of hospice care attitudes was (76.04±12.18) among these 270 nursing interns. Having cared for critically ill patients, receiving hospice care-related education, and experiencing the loss of relatives or friends in the past year were positive influencing factors for their hospice care attitudes, whereas avoidance of talking about death was a negative influencing factor. The total score of hospice care competence was (42.75±4.68). Having cared for critically ill patients and receiving hospice care-related education represented positive influencing factors for their hospice care competence. ConclusionThe hospice care attitudes and competence of nursing interns are all at moderate levels. It is necessary to strengthen education and training on hospice care for nursing interns, improve the ability of nurses, and provide assistance for the development of hospice care.
4.Cognitive reserve and social cohesion in influence on fall-related self-awareness among the elderly in community
Jiajun WEI ; Jia ZHANG ; Mengting OUYANG ; Nifang XIE ; Zhangjie SHI ; Xin SUN
Modern Clinical Nursing 2025;24(9):8-16
Objective To study the level of fall-related self-awareness among the elderly in community and to explore the influence of cognitive reserve and social cohesion on fall-related self-awareness,thereby providing a reference for developing targeted interventions.Methods Toally 500 old people in communities were recruited by convenience sampling in Hengyang between August and September 2024.Data were collected with the general information questionnaire,neighbourhood cohesion scale,self-awareness of falls in elderly scale,and cognitive reserve index questionnaire.Hierarchical multiple linear regression analysis was employed to explore the effects of cognitive reserve and social cohesion on fall-related self-awareness while controlling for demographic variables.Results A total of 467 valid questionnaires were returned.The score of fall-related self-awareness was 54.60±6.64(moderate level).Social cohesion scores was 29.84±5.52(moderate level),and cognitive reserve score was 93.27±10.83(moderate level).The cognitive reserve and social cohesion were both positively correlated with fall-related self-awareness(all P<0.01).Community integration accounted for 9.10%of its total variability,and cognitive reserve accounted for 5.70%of the total variability of fall vigilance,while controlling for variables such as body mass index(BMI),sleep quality,sedentary habits,fear of falling and financial resources.Conclusion The elderly in communities exhibit a low level of fall-related self-awareness.More attention to risk of falling is required along with developing targeted and individualised training programs aiming at improvement of cognitive reserve and social cohesion,thereby reducing the incidence of falls.
5.Current status of job competency of full-time healthcare-associated infec-tion management professionals in 31 provinces across China
Xin LIU ; Mengnai XIE ; Jihua SUN ; Hongfang SONG ; Fang LIU ; Guoai FAN ; Jia WEI ; Meng CAI
Chinese Journal of Infection Control 2025;24(3):354-360
Objective To understand the current status of the job competency of full-time healthcare-associated in-fection(HAI)management professionals in all levels and types of medical institutions across China,and provide in-formation and basis for professional training,competency improvement,and career planning.Methods The strati-fied sampling method was adopted to select HAI management professionals from medical institutions in 31 provin-cial-level administrative regions across the country as the research subjects.The designed content of questionnaire involved four parts,including the surveyed personnel's basic information,daily job competency assessment,satis-faction level towards the job,as well as opinions and suggestions on the management of full-time HAI management professionals.The assessment on daily job competency was divided into 13 dimensions,ranging from very incompe-tent to very competent in 5 levels.The scores of HAI management professionals with different professional back-grounds were compared and analyzed.Results A total of 8 709 valid questionnaires were collected,with 3 475 and 3 697 surveyed personnel from tertiary and secondary medical institutions,respectively,and 1 537 from primary or unclassified medical institutions.The overall average score for the competency assessment of full-time HAI manage-ment professionals was(4.17±0.80)points.The scores of professionals with different professional backgrounds,from high to low,were as follows:nursing([4.12±0.81]points),clinical medicine([4.07±0.86]points),pre-ventive medicine([3.93±0.92]points),laboratory medicine([3.88±0.93]points),pharmacy([3.86±0.94]points),and health management([3.85±0.95]points).For the core competency of HAI management professio-nals,such as monitoring and analyzing HAI cases,identifying and investigating HAI outbreaks,the assessment scores for professionals with medical backgrounds were the highest(both P<0.05).For the basic work of HAI prevention and control,such as checking and guiding the implementation of rules and regulations,guiding occupa-tional protection,management and communication,and implementing HAI management training,professionals with a nursing background had the highest assessment scores(all P<0.05).Full-time HAI management professionals were relatively satisfied with their training,while those with a background in preventive medicine had lower satisfac-tion with their training,career development,and job benefits(all P<0.05).Conclusion There are significant differences in the competency of HAI management professionals with different professional backgrounds.It is nece-ssary to optimize division of labor and leverage the strengths,providing ideas and models for promoting the construction of a specialized and professional HAI management team.
6.Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
Jie WANG ; Jian LIU ; Xiao-ting ZHU ; Yun-qiang LI ; Xin-yue ZHANG ; Fan LI ; Jia-li WU ; Wei LI ; Ming-quan LI
Chinese Traditional Patent Medicine 2025;47(6):1843-1852
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P<0.05,P<0.01);prolonged evasion latency(P<0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P<0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P<0.01);decreased levels of M2-type marker CD206(P<0.05);elevated levels of TNF-α and IL-1β(P<0.01);decreased expressions of IL-13 and IL-4(P<0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P<0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P<0.05,P<0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.
7.Changing resistance profiles of Haemophilus influenzae and Moraxella catarrhalis isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Hui FAN ; Chunhong SHAO ; Jia WANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Yunsheng CHEN ; Qing MENG ; Hong ZHANG ; Chun WANG ; Fang DONG ; Wenqi SONG ; Kaizhen WEN ; Yirong ZHANG ; Chuanqing WANG ; Pan FU ; Chao ZHUO ; Danhong SU ; Jiangwei KE ; Shuping ZHOU ; Hua ZHANG ; Fangfang HU ; Mei KANG ; Chao HE ; Hua YU ; Xiangning HUANG ; Yingchun XU ; Xiaojiang ZHANG ; Wenen LIU ; Yanming LI ; Lei ZHU ; Jinhua MENG ; Shifu WANG ; Bin SHAN ; Yan DU ; Wei JIA ; Gang LI ; Jiao FENG ; Ping GONG ; Miao SONG ; Lianhua WEI ; Xin WANG ; Ruizhong WANG ; Hua FANG ; Sufang GUO ; Yanyan WANG ; Dawen GUO ; Jinying ZHAO ; Lixia ZHANG ; Juan MA ; Han SHEN ; Wanqing ZHOU ; Ruyi GUO ; Yan ZHU ; Jinsong WU ; Yuemei LU ; Yuxing NI ; Jingrong SUN ; Xiaobo MA ; Yanqing ZHENG ; Yunsong YU ; Jie LIN ; Ziyong SUN ; Zhongju CHEN ; Zhidong HU ; Jin LI ; Fengbo ZHANG ; Ping JI ; Yunjian HU ; Xiaoman AI ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Xuesong XU ; Chao YAN ; Yi LI ; Shanmei WANG ; Hongqin GU ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Jihong LI ; Bixia YU ; Cunshan KOU ; Jilu SHEN ; Wenhui HUANG ; Xiuli YANG ; Likang ZHU ; Lin JIANG ; Wen HE ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(1):30-38
Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91%of the total clinical isolates and 4.07%of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89%were isolated from children and 33.11%were isolated from adults.More than 90%of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79%in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06%were isolated from children and 19.94%isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0%.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.
8.Regulation of ferroptosis susceptibility in acute myeloid leukemia cells by enolase ENO1
Jia-qi WAN ; Yue LI ; Xin-tong YANG ; Hong-wei PENG
Chinese Pharmacological Bulletin 2025;41(9):1711-1719
Aim To investigate the expression of al-pha-enolase 1(ENO1)in FLT3-mutated acute myeloid leukemia(AML)and its impact on prognosis,as well as to assess the influence of ENO1 on the antitumor effects of FLT3 inhibitors.Methods Data from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed to compare the expression differences of ENO1 in various tumors and normal tissues.ENO1 knockdown cells were con-structed using the AML cell line MOLM13.The impact of ENO1 on AML cell proliferation,apoptosis,and drug sensitivity was evaluated through CCK-8 assays,flow cytometry,drug synergy experiments,transcriptome se-quencing,and lipid peroxide and reactive oxygen spe-cies(ROS)levels were detected.Results The ex-pression level of ENO1 was significantly elevated in FLT3 internal tandem duplication mutation(FLT3-ITD)positive AML patients and was associated with poor prognosis.Knockdown of ENO1 significantly in-hibited AML cell proliferation and induced apoptosis.Inhibition of ENO1 significantly increased the chemo-sensitivity of AML cells to FLT3 inhibitors.Transcrip-tome sequencing analysis revealed differential expres-sion of genes in the NADPH oxidase-related pathway following ENO1 knockdown,and a positive correlation between ENO1 and glutathione peroxidase 4(GPX4)expression.Inhibition of ENO1 significantly increased the levels of lipid peroxides and ROS induced by FLT3 inhibitors.Conclusions High expression of ENO1 is significantly associated with poor prognosis in FLT3(+)AML.Inhibition of ENO1 can enhance the anti-tumor effects of FLT3 inhibitors by regulating the an-tioxidant defense capacity of AML cells,providing a new target and therapeutic strategy for the treatment of FLT3/ITD(+)AML.
9.Comparison of short-term safety and efficacy among total laparoscopic, laparoscopy-assisted, and open radical total gastrectomy after neoadjuvant therapy: a multicenter retrospective study
Xiaopeng GAO ; Jia YUAN ; Xianghuang MEI ; Zhijie FENG ; Xin GUO ; Gang JI ; Yanyang SONG ; Jiangpeng WEI
Chinese Journal of Gastrointestinal Surgery 2025;28(7):758-766
Objective:To evaluate the short-term safety and efficacy of total laparoscopic, laparoscopy-assisted, and open total gastrectomy in patients with gastric cancer who have undergone neoadjuvant therapy.Methods:In this retrospective cohort study, relevant clinical data on 243 patients who had undergone radical total gastrectomy after receiving neoadjuvant therapy were collected. These patients had been admitted to the First Affiliated Hospital of Air Force Medical University, Yuncheng Central Hospital of Shanxi Province, and Heji Hospital Affiliated to Changzhi Medical College between January 2020 and April 2024. Among them, 202 were male (83.1%) and 41 were female (16.9%), and their average age was 61.3±8.1 years. The patients were allocated to three groups according to surgical procedure: total laparoscopic (68 cases), laparoscopic- assisted (79 cases), and open surgery (96 cases). We compared relevant baseline characteristics, neoadjuvant treatment, intraoperative and postoperative conditions, postoperative histopathological findings, and related complications between these three groups.Results:There were no statistically significant differences in baseline characteristics or neoadjuvant treatment between the three groups (all P>0.05). The operative time was longer in the total laparoscopic group than in the laparoscopic-assisted and open surgery groups (267.7±37.9 minutes vs. 243.9±38.3 minutes vs. 219.7±41.2 minutes, respectively; F=7,112.278; P<0.001). However, more lymph nodes were harvested in the total laparoscopic group than in the laparoscopic-assisted and open surgery groups (27.8±4.8 vs. 27.4±6.3 vs. 27.2±5.1, respectively; F=6.042; P=0.002). Additionally, the total laparoscopic group had shorter times to first postoperative flatus (2.3±0.7 days vs. 2.4±0.7 days vs. 2.6±0.6 days, respectively; F=5.094; P=0.006] and first postoperative bowel movement (2.9±0.5 days vs. 3.0±0.6 days vs. 3.0±0.6 days, respectively; F=3.929; P=0.020). There were no statistically significant differences in intraoperative blood loss, intraoperative transfusion rates, postoperative intensive care unit admission rates, maximum tumor diameter, number of positive lymph nodes dissected, TNM stage, time to first postoperative oral intake, time to drain removal, or length of hospital stay between the three groups (all P>0.05). Among the 243 patients, 22 developed postoperative complications, making the overall complication rate 9.1%. Six patients (8.8%) in the total laparoscopic group developed complications, comprising two (2.9%) Grade IIIa Clavien-Dindo complications. One of these patients (1.5%) was readmitted within 30 days due to complications. Seven patients (8.9%) in the laparoscopic-assisted group developed complications, comprising two (2.5%) Grade IIIa Clavien-Dindo complications. One of these patients was readmitted within 30 days and another was within 90 days due to complications. Nine patients (9.4%) in the open surgery group developed complications, comprising four (4.2%) Grade IIIa Clavien-Dindo complications. Two patients (2.1%) were readmitted within 30 days and another (1.0%) within 90 days due to complications. There were no statistically significant differences among the three surgical approaches in overall postoperative complication rates, Clavien-Dindo grades, or readmission rates 30 and 90 days postoperatively (all P>0.05). Conclusions:In patients with gastric cancer who have undergone neoadjuvant therapy, there are no significant differences in the overall safety and short-term effectiveness of the three surgical procedures. Although the operative time is longer for total laparoscopic total gastrectomy, this procedure offers the advantages of faster postoperative recovery and earlier resumption of feeding.
10.Effects of Jiedu Yizhi Formula on neuroinflammation in a mouse model of Alzheimer's disease via PI3K/Akt/mTOR signaling pathway
Jie WANG ; Jian LIU ; Xiao-ting ZHU ; Yun-qiang LI ; Xin-yue ZHANG ; Fan LI ; Jia-li WU ; Wei LI ; Ming-quan LI
Chinese Traditional Patent Medicine 2025;47(6):1843-1852
AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P<0.05,P<0.01);prolonged evasion latency(P<0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P<0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P<0.01);decreased levels of M2-type marker CD206(P<0.05);elevated levels of TNF-α and IL-1β(P<0.01);decreased expressions of IL-13 and IL-4(P<0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P<0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P<0.05,P<0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

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