1.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
2.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
3.Jujuboside A Improves Cognitive Function in Rat Model of VCI via PI3K/Akt Signaling Pathway
Zixuan HUANG ; Shuo YANG ; Jiaqi ZHOU ; Gengchao ZHANG ; Qiuyun YOU ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):107-114
ObjectiveTo investigate the effects of jujuboside A (JuA) on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment (VCI) and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group (n=10), a blank control group (n=10), and a modeling group (n=30). The rats in the modeling group underwent bilateral carotid artery ligation (2-VO) for the modeling of VCI. After stabilization, the VCI rats were randomized into model, JuA (20 mg·kg-¹), and donepezil (0.45 mg·kg-¹) groups. After 4 weeks of gavage, the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β (GSK-3β), cAMP response element-binding protein (CREB), B cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β, p-GSK-3β, p-CREB, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group, the model group exhibited declines in the learning and memory abilities (P<0.01), neuronal damage and decreased neurons in the hippocampal CA1 region (P<0.01), up-regulation in the mRNA level of GSK-3β (P<0.01), and down-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2, as well as the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.01). In comparison to the model group, both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities (P<0.05, P<0.01), with reduced neuronal damage and increased neurons (P<0.05, P<0.01). In addition, the two groups showed down-regulation in the mRNA level of GSK-3β (P<0.01) and up-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2 and the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.05, P<0.01). There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities, neuron count, and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway, reducing the apoptosis of hippocampal neurons, and alleviating the hippocampal neuronal damage.
4.Analysis of a questionnaire survey on several issues related to the Chinese expert consensus on cerebrovascular ultrasound detection
Jingxin ZHONG ; Aihua OU ; Yang HUA
Chinese Journal of Cerebrovascular Diseases 2024;21(11):752-758
Objective To investigate the current status,diagnostic difficulties,and the necessity of formulating a consensus on several issues of cerebrovascular ultrasound examination in China.Methods A network questionnaire survey was conducted to investigate several problems of cerebrovascular ultrasound and the needs of expert consensus among practitioners of transcranial Doppler(TCD)ultrasound and transcranial color coded Doppler(TCCD)ultrasound in medical institutions.The questionnaire covered the basic information of the respondent group,including the region where the medical institution was located(Q1),the level of the medical institution(Q2),the scope of practice of TCD or TCCD practitioners(Q3),title(Q4);the assessment mode of cerebrovascular and cervical vascular(Q5);the general demand for expert consensus(Q6)and TCD diagnosis-related issues(Q7-Q17).There were three dimensions of TCD diagnosis-related issues(diagnostic criteria,multi-dimensional comprehensive assessment,and dynamic monitoring during the perioperative period of angioplasty),with a total of 11 items(Q7-Q17:intracranial artery stenosis or occlusion,vascular development anomalies,side branch circulation judgment,ultrasound dynamic monitoring after angioplasty,cerebral vasospasm,contrast-enhanced TCD examination,etc.).At the same time,open-ended questions were also set up:the most important content to be improved in cerebrovascular ultrasound(Q18).The reliability analysis of the questionnaire was used to assess the reliability,with Cronbach's α coefficient ≥0.7 considered as good reliability.The validity evaluation was conducted by factor analysis.The comparison of the demand for each item under different conditions was conducted by x2 test,and the Kruskal-Wallis H test was used to compare ranked data among different groups.Results A total of 1 395 complete and valid questionnaires were collected,involving TCD or TCCD practitioners from 31 provinces,autonomous regions,and municipalities(there was no response from the Xizang Autonomous Region),which had a certain representativeness.Survey reliability evaluation:Cronbach's α coefficient=0.917(F=132.702,P<0.01).Factor analysis,KOM=0.930(x2=8 478.844,P<0.01),the cumulative contribution rate was 70.600%when taking into account three factors.Among the respondents,the proportion of those from tertiary-level grade A hospitals was the highest(64.2%[896/1 395]);the distribution of titles was dominated by those of attending physicians(48.5%[676/1 395]),followed by senior titles(37.2%[519/1 395]);among the respondents,66.6%(929/1 395)said they urgently needed expert consensus,while 32.7%(456/1 395)said they needed to improve existing standards.There were significant differences in the needs for expert consensus and each item across different regions,professional titles and evaluation models(all P<0.05).Conclusions The questionnaire have high reliability and validity.There is an urgent need for expert consensus on several issues related to cerebrovascular ultrasound among the respondents.The establishment of expert consensus would contribute to standardized and precise evaluation system,thereby promoting quality control management and standardization of cerebrovascular ultrasound practices.
5.Correlation between subclavian artery stenosis disease classification and posterior circulation ischemia
Yang LIU ; Aihua HUANG ; Xiongwei ZHANG ; Ying WANG ; Yonghan LIANG ; Guangyu WANG ; Chenxi TAN ; Feng QIU
Chinese Journal of Neuromedicine 2024;23(11):1094-1099
Objective:To explore the correlation between subclavian artery stenosis disease (SASD) classification and posterior circulation ischemia.Methods:A retrospective study was performed; the clinical data, and Doppler vascular ultrasound and vascular imaging results of 81 SASD patients, admitted to Cerebrovascular Stenosis Diagnosis and Treatment Center, Second Affiliated Hospital of Qiqihar Medical College and Department of Neurology, Rocket Force Specialty Medical Center from May 2018 to August 2023, were collected. SASD was categorized into 2 types (single type and concurrent type) based on the presence or absence of other posterior circulation artery (basilar artery, vertebral artery, or subclavian artery distal segment) stenosis/occlusion, and into 3 groups (non-posterior circulation ischemia group, posterior circulation transient ischemic attack group and posterior circulation cerebral infarction group) based on the presence or absence of posterior circulation ischemia. Blood stealing pathways in different SASD classifications were analyzed, and correlation of SASD classification with posterior circulation ischemia was discussed.Results:Single-type SASD was noted in 44 patients (54.3%), mainly initiating blood stealing through the vertebral artery to the vertebral artery and then to the subclavian artery ( n=26); concurrent-type SASD was noted in 37 patients (45.7%), mainly initiating blood stealing through the occipital artery to the costocervical trunk and then to the subclavian artery ( n=10). Sixty-five patients (80.2%) were into the non-posterior circulation ischemia group, 4 (4.9%) into the posterior circulation transient ischemic attack group and 12 (14.8%) into the posterior circulation cerebral infarction group. Among the 44 patients with single-type SASD, 39 did not have posterior circulation ischemia, and 3 had posterior circulation cerebral infarction. Among the 37 patients with concurrent-type SASD, 26 did not have posterior circulation ischemia, and 9 had posterior circulation cerebral infarction. Conclusion:Initiation of blood stealing in SASD patients is related to SASD classification, and concurrent-type SASD patients trend to have posterior circulation ischemia.
6.A Structural Equation Model of the Relationship Between Symptom Burden, Psychological Resilience, Coping Styles, Social Support, and Psychological Distress in Elderly Patients With Acute Exacerbation Chronic Obstructive Pulmonary Disease in China
Mengfei LAN ; Li YANG ; Hongqiang ZHANG ; Aihua SU ; Qiling YIN ; Jiaoyue LI
Asian Nursing Research 2024;18(3):231-237
Purpose:
The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, current researches are insufficient to clarify the correlation among these relevant factors. This study examined the effects of symptom burden, psychological resilience, coping styles, and social support on psychological distress.
Methods:
Two hundred fifty five elderly patients with AECOPD were conveniently selected in Taian, Shandong Province. The General Information Questionnaire, Distress Thermometer, The Revised Memorial Symptom Assessment Scale, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale were used to investigate. The relationship among factors was estimated by using a structural equation model.
Results:
Psychological distress score of elderly patients with AECOPD was (5.25 ± 1.01); coping styles, psychological resilience, symptom burden, and social support directly affected psychological distress (thedirect effects were À.93, .17, .17, and À.09); coping styles had the largest total effect on psychological distress (the total effect was À.93); psychological resilience indirectly affected psychological distress through coping styles (the indirect effect was À.74); symptom burden indirectly affected psychologicaldistress through psychological resilience (the indirect effect was .25); social support indirectly affected psychological distress through symptom burden, psychological resilience, and coping styles (the indirecteffect was À.80).
Conclusion
The psychological distress of elderly patients with AECOPD is at a moderate level; coping styles, psychological resilience, and social support have positive effects on alleviating the psychological distress of elderly patients with AECOPD; symptom burden is negatively correlated with psychological distress.Healthcare professionals should pay more attention to elderly patients with AECOPD who are particularly prone to experience higher levels of psychological distress, especially in the presence of low coping style, limited psychological resilience, inadequate levels of social support, and high symptom burden.
7.A Structural Equation Model of the Relationship Between Symptom Burden, Psychological Resilience, Coping Styles, Social Support, and Psychological Distress in Elderly Patients With Acute Exacerbation Chronic Obstructive Pulmonary Disease in China
Mengfei LAN ; Li YANG ; Hongqiang ZHANG ; Aihua SU ; Qiling YIN ; Jiaoyue LI
Asian Nursing Research 2024;18(3):231-237
Purpose:
The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, current researches are insufficient to clarify the correlation among these relevant factors. This study examined the effects of symptom burden, psychological resilience, coping styles, and social support on psychological distress.
Methods:
Two hundred fifty five elderly patients with AECOPD were conveniently selected in Taian, Shandong Province. The General Information Questionnaire, Distress Thermometer, The Revised Memorial Symptom Assessment Scale, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale were used to investigate. The relationship among factors was estimated by using a structural equation model.
Results:
Psychological distress score of elderly patients with AECOPD was (5.25 ± 1.01); coping styles, psychological resilience, symptom burden, and social support directly affected psychological distress (thedirect effects were À.93, .17, .17, and À.09); coping styles had the largest total effect on psychological distress (the total effect was À.93); psychological resilience indirectly affected psychological distress through coping styles (the indirect effect was À.74); symptom burden indirectly affected psychologicaldistress through psychological resilience (the indirect effect was .25); social support indirectly affected psychological distress through symptom burden, psychological resilience, and coping styles (the indirecteffect was À.80).
Conclusion
The psychological distress of elderly patients with AECOPD is at a moderate level; coping styles, psychological resilience, and social support have positive effects on alleviating the psychological distress of elderly patients with AECOPD; symptom burden is negatively correlated with psychological distress.Healthcare professionals should pay more attention to elderly patients with AECOPD who are particularly prone to experience higher levels of psychological distress, especially in the presence of low coping style, limited psychological resilience, inadequate levels of social support, and high symptom burden.
8.Efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children:meta-analysis of single-group rate
Caixia TU ; Danyang REN ; Jianling SHEN ; Yunwei LI ; Yanming YANG ; Aihua YAN ; Lin LI ; Huiying LI
China Pharmacy 2024;35(15):1893-1898
OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children, and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed, The Cochrane Library, Embase, CNKI, VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction, the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial, and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally, 18 one-arm studies were included, with a total of 1 424 children. The results showed that compared with before additional treatment, the proportion of patients with seizures-free (proportion of patients with seizure reduction of 100%) was 24%[95%CI (0.18,0.32), P<0.000 01] after conversion; the proportion of patients with seizure reduction ≥75% was 32%[95%CI(0.25,0.40), P<0.000 1] after conversion; the proportion of patients with seizure reduction ≥50% was 53%[95%CI(0.44,0.61),P<0.000 01]; the proportion of patients with seizure reduction <50% or no change was 35%[95%CI(0.24,0.49),P=0.04] after conversion; the proportion of patients with seizure increase was 9%[95%CI(0.05,0.18),P<0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI(0.23,0.40),P<0.000 1] after conversion; the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI(0.07, 0.15), P<0.000 01] after conversion. The common adverse drug reactions were drowsiness, fatigue and behavior change, etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children, but its adverse effects should be vigilant.
9.Research progress on influencing factors and training of nurses'compassion
Jiaoyue LI ; Li YANG ; Aihua SU ; Mengfei LAN ; Hongqiang ZHANG ; Yixuan QI
Chinese Journal of Nursing 2024;59(3):371-377
Compassion is an important part of nurses'professional quality,and it is also the basis of effective nurse-patient communication and humanistic care.Improving nurses'compassion is helpful to provide high-quality nursing services to patients.This study reviews the definition of compassion,the factors affecting compassion and the training methods to improve compassion,analyzes the shortcomings of existing training methods,and puts forward the prospects for future research,so as to provide a theoretical foundation for future compassion training among nurses.
10.Analysis of the suspected cases of measles and rubella in Pudong New Area of Shanghai, 2013‒2022
Xiao WANG ; Aihua ZHANG ; Huiqin FU ; Yuying YANG ; Xiaoxian CUI ; Lipeng HAO ; Yanqiu ZHOU ; Lifeng PAN
Shanghai Journal of Preventive Medicine 2024;36(6):534-539
ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022, and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022, among which the positive rate of measles IgM antibody was 33.55% (513/1 529). The highest positive rate (20.73%) was from March to May , and the positive rate of rubella IgM antibody was 6.80% (104/1 529). The positive rate of both IgM was higher in males than that in females (P<0.05). The IgM against measles was mainly detected in 0‒ years old (63.16%, 96/152) and 20‒ years old (45.61%, 161/353). The IgM against rubella was mainly detected in 10‒20 years old (27.27%, 18/66). The IgM antibody could be detected more easily from 4 to 28 days after eruption, and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years (2013‒2019). There were 2 D8 genotype strains, and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles, and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children, in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization, and the surveillance of imported measles cases should be strengthened.

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