1.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
2.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
3.Bioinformatics Analysis and Validation of Cuproptosis-related Genes in Wilson Disease
Zhuang TAO ; Meixia WANG ; Shuai KANG ; Jipeng LIU ; Rui WANG ; Jiafeng ZHOU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):124-131
ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease (WD) through bioinformatics analysis and clinical validation,providing implications and directions for the diagnosis and treatment of WD. Methods(1) Screening of target genes: The differentially expressed genes (DEGs) between WD and healthy control were obtained from GeneCards,and the cuproptosis-related genes were obtained from Gene Expression Omnibus (GEO) and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses,the specific biological process,functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.(2)Validation of target genes: The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results(1) A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO,and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection,including three up-related genes(SQSTM1,MIF1,and TAX1BP1) and nine down-regulated genes(CP,SERPINE1,AOC3,GPX4,SLC27A5,VEGF-A,PDHB,PDK1,and ATP7B).The common target genes were mainly enriched in monocarboxylic acid metabolism,oxidoreductase activity,negative regulation of molecular functions,which mainly involved HIF-1,ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1,SERPINE1,VEGFA,and AOC3 in WD.(2)A total of 30 blood samples were collected,including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers,WD patients had down-regulated mRNA levels of SERPINE1,GPX4,SLC27A5,and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1(P<0.05). ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD,which can provide a new target for the diagnosis and treatment of WD.
4.Assignment of chemical exposure parameter in occupational health risk assessment models: Key consideration
Jiayun DING ; Meixia LIU ; Jiming ZHANG ; Yan YIN ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2025;42(4):497-502
The core idea of occupational health risk assessment models is to systematically evaluate occupational health risks according to target hazard characteristics and relevant exposure levels of workers. Occupational exposure assessment is based on concentration, frequency, exposure time, and other indicators that indicate actual exposure of workers to occupational hazards, which is a critical component of health risk assessment. However, the accuracy and comparability of assessment results are affected by differences in parameter assignment for exposure assessment across different studies, as well as insufficient emphasis on multiple occupational hazard exposure. This review aimed to explore the assignment and standardization of exposure assessment parameters for occupational health risk assessment modeling, and systematically sorted out the meaning, assignment methods, and sources of exposure assessment related parameters in commonly used occupational health risk assessment models, with the goal of providing researchers with standardized assessment tools to enhance the scientific rigor and practicality of occupational health risk assessments. Considering the individual differences and temporal fluctuations in occupational exposure, it is recommended that researchers should adopt appropriate sampling strategies, reasonably select sample subjects and time based on the division of similar exposure group (SEG), and conduct statistical inference on the obtained data to derive representative exposure parameters. For combined exposure to chemicals with similar toxic effects, the health risk assessment methods are relatively mature. However, the assessment of combined exposure to hazards with different properties and health effects still lacks scientific authority and needs further research and discussion.
5.Simulation analysis of the protective performance of barium sulfate mortar against positron nuclide γ-rays
Zhiqiang XU ; Huaixin NI ; Jiwu GENG ; Lichun LI ; Zaoqin ZHANG ; Shibiao SU ; Meixia WANG ; Ming LIU
Chinese Journal of Radiological Health 2025;34(2):209-213
Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide 18F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide 18F was 1.339 4×10−1 μSv·m2/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by 18F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm3 mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were
6.Application and comparison of three risk assessment methods for occupational health risk assessment of dust in a sanitary ceramic product manufacturing enterprise
Song JIANG ; Yuanqiang JIANG ; Meixia LIU
Shanghai Journal of Preventive Medicine 2024;36(2):179-185
ObjectiveThree methods were applied to conduct occupational health risk assessment for the working positions exposed to silicon dusts in a sanitary ceramic manufacturing factory, and the evaluation results were compared to explore the applicability of different occupational health risk assessment methods. MethodsOne large sanitary ceramic product manufacturing enterprise in Songjiang District, Shanghai was selected to conduct occupational health risk assessment for the working positions exposed to silicon dusts, using occupational hazard risk index evaluation method, exposure ratio evaluation method, and International Council on Mining and Metals (ICMM) quantitative occupational health risk assessment method . The consistency of the evaluation results of the three methods was tested using weighted Kappa method. ResultsFourteen working positions exposed to silicon dusts were identified, and three positions had excessive dust concentration: composite forming position of phase 2 workshop (0.80 mg·m-3), addition forming position of phase 2 workshop (1.00 mg·m-3), and glazing position of 1F in phase 2 workshop (1.50 mg·m-3), with an excessive rate of 21.42%. The occupational hazard risk index evaluation method assessed 6 positions with no harm, 6 positions with mild harm, and 2 positions with moderate harm. The ICMM quantitative occupational health risk assessment method assessed 6 positions with potential risks, 2 positions with tolerable risks, and 6 positions with intolerable risks. The exposure ratio evaluation method assessed 8 positions with medium risk, 5 positions with high risk, and 1 position with extremely high risk. The consistency test results of the three evaluation methods were poor. The Kappa coefficient between the occupational hazard risk index evaluation method and the ICMM quantitative occupational health risk assessment method was 0.15. The Kappa coefficient between the occupational hazard risk index evaluation method and the exposure ratio evaluation method was -0.09. The Kappa coefficient between the ICMM quantitative occupational health risk assessment method and the exposure ratio evaluation method was 0.04. The RR values obtained by the three evaluation methods were significantly correlated: the correlation coefficients between RRICMM quantitative assessment method and RRexposure ratio evaluation method, RROccupational hazard risk index evaluation method and RRICMM quantitative assessment method, RROccupational hazard risk index evaluation method and RRexposure ratio evaluation method were 0.915, 0.604, and 0.594, respectively. The correlation between the assessment result level and CTWA was strong. ConclusionThe occupational hazard risk index evaluation method is suitable for the working positions with low silicon dust exposure concentration, the ICMM quantitative occupational health risk assessment method and the exposure ratio evaluation method are suitable for the positions with high silicon dust exposure concentration, but all these three evaluation methods have limitations. It is more reasonable to use multiple methods at the same time in actual evaluation work.
7.Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation.
Haohao ZHANG ; Lijuan SUN ; Zhixin ZHAO ; Yao ZHOU ; Yuyao LIU ; Nannan ZHANG ; Junya YAN ; Shibo WANG ; Renlong LI ; Jing ZHANG ; Xueying WANG ; Wenjiao LI ; Yan PAN ; Meixia WANG ; Bing LUO ; Mengbin LI ; Zhihong SUN ; Yongxiang ZHAO ; Yongzhan NIE
Chinese Medical Journal 2024;137(1):120-122
8.Study on relationship between hemoglobin glycation index and metabolic syndrome and its components
Yali ZHAO ; Meixia XIAO ; Yan LIU ; Zhiping ZENG ; Shengming SHI
China Modern Doctor 2024;62(16):61-65
Objective To investigate the relationship between hemoglobin glycation index(HGI)and metabolic syndrome(MS)and its components.Methods A cross-sectional study was conducted to randomly select 823 patients from the First People's Hospital of Huzhou from September 2022 to September 2023.HGI is calculated based on fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)values.The patients were divided into low HGI group(HGI<-0.250%,274 cases),medium HGI group(-0.250%≤HGI≤0.214%,275 cases)and high HGI group(HGI>0.214%,274 cases)by HGI quantile method.The general data and metabolic indexes of each group were compared,and the correlation between HGI and MS and its components was analyzed by multiple Logistic regression.Results With the increase of HGI level,the prevalence rate of MS showed an upward trend(P<0.05).The prevalence rate of MS in low,medium and high HGI groups was 24.8%,42.5%and 55.5%,respectively.Multiple Logistic regression analysis showed that elevated HGI level was risk factor for MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia(P<0.05).The risk of MS,central obesity,hypertension,hyperglycemia,hypertriglyceridemia and low high-density lipoprotein hyperlipidemia in high HGI group was 4.005 times(95%CI:2.763-5.808),3.765 times(95%CI:2.604-5.443),1.596 times(95%CI:1.089-2.337),2.655 times(95%CI:1.809-3.895),2.024 times(95%CI:1.404-2.918)and 2.247 times(95%CI:1.537-3.284)of that in low HGI group,respectively.Conclusion HGI is related to MS and its components,and HGI may be a new indicator to prevent and monitor MS.
9.Clinical study of Jiaotai Shugan decoction in adjuvant treatment of type 2 diabetes mellitus complicated with depression with liver qi stagnation type
Yongjin LIU ; Bo DU ; Huijuan ZHAN ; Jing LIU ; Yan WANG ; Anping WANG ; Ying HUA ; Meixia XIE
China Modern Doctor 2024;62(21):95-98,103
Objective To investigate the clinical effect of Jiaotai Shugan decoction in adjuvant treatment of type 2 diabetes mellitus(T2DM)complicated with depression with liver qi stagnation type.Methods From June 2022 to June 2023,90 patients with T2DM complicated with depression with liver qi stagnation type treated in the Second People's Hospital of Lishui City were selected,who were randomly divided into control group and observation group,with 45 cases in each group.Both groups were treated with basic treatment of diabetes,control group was given escitalopram to improve the emotion,while observation group was further given Jiaotai Shugan decoction.After 8 weeks,the clinical effective rate were evaluated by Hamilton depression scale-24(HAMD-24)and patient health questionnaire-9(PHQ-9)scores,the levels of 5-hydroxytrytamine(5-HT),noradrenaline(NE),brain-derived neurotrophic factor(BDNF),fasting blood glucose(FPG),2-hour postprandial blood glucose(2hPG)and haemoglobinA1c(HbA1c)were detected,and adverse reactions were recorded.Results The clinical total effective rates of observation group was higher than that of control group,and the difference was statistically significant(P<0.05).8 weeks after treatment,HAMD-24 and PHQ-9 scores of observation group were lower than those of control group(P<0.01).The levels of 5-HT,NE and BDNF of observation group were higher than those of control group(P<0.01).The levels of FPG,2hPG and HbA1c in observation group were lower than those in control group(P<0.01);There was no significant difference in adverse reactions between two groups(P>0.05).Conclusion Modified Jiaotai Shugan decoction is effective in treating T2DM complicated with depression with liver qi stagnation type,can reduce HAMD-24 and PHQ-9 scores,increase the levels of 5-HT,NE,BDNF,and reduce the levels of FPG,2hPG,HbA1c.There was no obvious adverse reactions.
10.Research on intake management in primipara labor analgesia during childbirth
Min XU ; Jing GAO ; Huilan ZHAO ; Meixia WANG ; Ruifen JIAO ; Xueqin LIU ; Xiao CHEN
Journal of Clinical Medicine in Practice 2024;28(4):79-83
Objective To investigate the effect of dietary intake on the childbirth outcomes of primipara women with full-term labor analgesia. Methods A total of 400 primipara women with full-term labor analgesia were randomly divided into observation group and control group. The observation group received intake management and individualized dietary guidance, while the control group ate and drank according to their own wishes. The childbirth quality, the incidence of vomiting, the use of oxytocin due to uterine atony, the rate of intrapartum fever, the rate of perineal incision, the rate of cesarean section, the rate of vaginal assisted delivery, and the rate of postpartum hemorrhage were compared between the two groups. The duration of the first stage of labor, the duration of the second stage of labor, the duration of labor analgesia, and the amount of postpartum hemorrhage within 2 hours were also compared. Neonatal Apgar score, random blood glucose, umbilical artery blood pH value, umbilical artery blood lactic acid (Lac) value, the incidence of neonatal asphyxia, the incidence of neonatal fever, and the incidence of neonatal hypoglycemia were compared between the two groups. Results The observation group had lower incidences of vomiting, oxytocin use rate due to uterine atony, intrapartum fever rate, perineal incision rate, transferring cesarean section rate, and vaginal assisted delivery compared to the control group(


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