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.Role of TLR4/ERK1/2 signaling pathway in decidual tissue of unexplained spontaneous abortion
Na LI ; Zhaojin LUAN ; Meixia YANG ; Xiaoling GONG ; Ziwei ZHAO ; Fang SONG
Chinese Journal of Immunology 2024;40(3):503-506
Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.
4.Medical equipment management practice in the establishment of a tertiary-A occupational disease specialized hospital
Meixia WANG ; Ruizhu FANG ; Diexian ZHONG ; Xu LIANG ; Liushan XIONG ; Shencheng HUANG ; Liping LIU ; Xiaozhou SU ; Hailin LIAO
China Occupational Medicine 2024;51(6):682-687
Passing the hospital grading evaluation, establishing a tertiary-A specialized hospital for occupational diseases, enhancing hospital's internal quality and sustainable development, and continuously improving medical service quality are important measures to promote the high-quality development of hospitals. The evaluation standards for occupational disease specialized tertiary-A hospital require standardized, scientific, and sustainable management of medical equipment. Guangdong Province Hospital for Occupational Disease Prevention and Treatment is the first tertiary-A hospital for occupational diseases specialized in Guangdong Province. Relative regulation on medical equipment management was systematically reviewed based on the requirement of tertiary-A specialized hospital for occupational diseases during hospital grading evaluation process. Building and completing the medical equipment management system, standardizing and strengthening government procurement management, completing the configuration management and safety management of large-scale medical equipment, strengthening the effectiveness analysis and evaluation of large equipment, enhancing training on medical equipment usage, establishing emergency allocation systems for first-aid and life support medical equipment, and forming a medical equipment quality and safety management team is the measure to systematically improve and implement each item in various regulation for the full lifecycle management of medical equipment. It provides vital support in passing the tertiary-A hospital evaluation for hospitals. During the hospital grading evaluation process, each issue identified in medical equipment management was addressed and improved. This process continuously enhanced the hospital's medical equipment management level, ensured the safe and effective use of medical equipment, and improved the quality of medical services, laying a solid foundation for the hospital to become a high level specialized medical institution for occupational diseases.
5.Application effect of intermittent fasting combined with diversified management mode in weight loss of overweight and obese people
Fang CHEN ; Zhixue GUO ; Shaoting WANG ; Zhong PAN ; Hongmei DONG ; Xin FENG ; Xizhuo WANG ; Meixia LIU ; Xiaoyong MA
Journal of Clinical Medicine in Practice 2024;28(7):72-74
Objective To explore the effect of intermittent fasting combined with diversified management mode on weight loss of overweight and obese people. Methods A total of 120 overweight and obese patients were selected as research objects, and randomly divided into control group (
6.Sexually transmitted infections (STIs) and related factors among pregnant women with non-local household registration in Xuhui District, Shanghai
Jiangfan YIN ; Fang FANG ; Yang LIU ; Ming LIN ; Meixia YANG ; Yibiao ZHOU
Shanghai Journal of Preventive Medicine 2023;35(2):110-115
ObjectiveTo study the sexually transmitted infections (STIs) in pregnant women with non-local household registration in Xuhui District and analyze the risk factors for STIs. MethodsFrom April 2020 to March 2022, pregnant women with non-local household registration who received their first prenatal examination in a general hospital in Shanghai Xuhui District were selected to conduct a status survey of STIs. Logistic regression model was used to analyze the influencing factors of bacterial vaginitis and ureaplasma uaplasma infection. ResultsThe top three infection rates in the pregnant women were Ureaplasma urealyticum (13.2%), bacterial vaginosis (9.8%) and mycotic vaginitis (4.7%). Age between 25 and 35 years (aOR=0.53,95%CI: 0.28‒0.98) and monthly income ≥8 000 yuan (aOR=0.30,95%CI: 0.11‒0.82) were significantly correlated with ureaplasma uaplasma infection. Pregnancy number of 2 (aOR=4.95, 95%CI: 1.59‒15.46), first sexual relationship occurred before marriage (aOR=2.83, 95%CI: 1.04‒7.74), husband's alcoholism (aOR=3.83, 95%CI: 1.08‒13.56), high school education (aOR=0.27, 95%CI: 0.08‒0.93), and husband's travel history (aOR=0.30, 95%CI: 0.12‒0.79) were significantly correlated with bacterial vaginitis. ConclusionPregnant women with more gestation times, first sexual intercourse before marriage and husband with heavy drinking are more likely to be infected with bacterial vaginosis. Pregnant women with younger age and lower income are more likely to be infected with Ureaplasma urealyticum. Follow-up and monitoring should be strengthened in these groups.
7.The effects of observing good swallowing on the swallowing ability of stroke survivors
Ming ZENG ; Jingmei MA ; Xudong GU ; Yunhai YAO ; Meihong ZHU ; Minmin JIN ; Meixia YANG ; Bihua ZHU ; Fang SHEN ; Shuzhen HU ; Jianming FU
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(2):116-121
Objective:To observe the effect of observing good swallowing on the swallowing action of stroke survivors with dysphagia.Methods:Eighteen stroke survivors with dysphagia were randomly divided into a treatment group ( n=9) and a control group ( n=9). In addition to routine swallowing rehabilitation therapy, the treatment group was asked to simulate swallowing after watching a video of normal people′s swallowing action. They did so 5 times a week for 10 minutes, while the control group just watched landscape videos at the same time. The treatment lasted 8 weeks. Before and after the treatment, both groups were assessed using the eating assessment tool (EAT-10), the functional oral intake scale (FOIS) and the penetration and aspiration scale (PAS). Functional magnetic resonance imaging (fMRI) was also used to observe their swallowing action. Results:There was no significant difference between the two groups in any of the measurements before the treatment. After the 8 weeks of treatment the average EAT-10, FOIS and PAS scores of the treatment group were all significantly better than before the treatment and better than the control group′s averages at the time. fMRI showed significantly more areas activated in the precuneus, parietal lobe, posterior central gyrus, BA7, BA5, frontal lobe and paracentral lobule in the treatment group compared with before the intervention and also more than in the control group.Conclusions:Observing proper swallowing action can improve dysphagia and activation of the swallowing-related brain areas of stroke survivors.
8.Investigation and Analysis of Current Situation of Human Research Ethical Management in Beijing Medical and Health Institutions
Zhengjuan HU ; Shuang MU ; Meixia WANG ; Xueqin WANG ; Mingjie ZI ; Zhuoran ZHANG ; Yingwei SUN ; Xiaolong MA ; Fang LIU ; Yiting LI
Chinese Medical Ethics 2018;31(2):230-235
Through the questionnaire survey on the current situation of human research ethical management in Beijing medical and health institutions, this paper analyzed the problems existing in ethical management of Beijing medical and health institutions and put forward corresponding countermeasures and suggestions. The results showed that overall status of human research ethical management in Beijing medical and health institutions was satisfying. But the ethical management levels of different types of medical and health institutions were quite different, and medical and health institutions, health family planning administration departments and academic teams should all make corresponding contributions.
9.Thoughts on Application of Evaluation Index System on Human Research Ethics Management in Beijing Medical Institutions
Zhengjuan HU ; Yiting LI ; Fang LIU ; Xiaoxia PENG ; Yingwei SUN ; Xiaolong MA ; Mingjie ZI ; Zhuoran ZHANG ; Meixia WANG ; Shuang MU
Chinese Medical Ethics 2017;30(6):737-741
Objective:This thesis aims to construct the evaluation index system ethics management in Beijing medical institutions for application research.Method:The author applied the evaluation system which was agreed and adjusted by expert groups in four medical and health institutions.Result:After three rounds of expert groups have reached the agreement,the Evaluation Index System on Human Research Ethics Management in Beijing Medi-cal Institutions is established,which contains 6 first-class indicators,16 second-class indicators and 39 third-class indicators.The application on four medical and health institutions show that the evaluation index system is practical,operable and is of high degree of distinction.Conclusion:The evaluation index system is scientific,rea-sonable,practical and is of high degree of validity,credibility and distinction.
10.Research on spatiotemporal spread of avian influenza A(H7N9) virus based on discrete geographic information
Meixia WANG ; Manqiong YUAN ; Ya FANG
Chinese Journal of Epidemiology 2016;37(11):1491-1496
Objective To establish a dynamic spatiotemporal spread modes of influenza A(H7N9) virus by using discrete geographic information and explore the spatiotemporal transmission of the virus.Methods The gene sequences of H7N9 virus isolated from human in China,which were available from Global Initiative on Sharing Avian Influenza Data (GISAID),were used in alignment by using software BioEdit 7.0.Spatiotcmporal spread model of H7N9 virus was established in a Bayesian statistical framework by using software BEAST 1.8.2.The symmetric substitution model and Bayesian stochastic search variable selection (BSSVS) were used to infer and verify the historical transmission route of H7N9 virus.Finally the spatiotemporal transmission route was presented by Google Earth software.Results The transmission of avian influenza A (H7N9) virus originated in Shanghai and Hangzhou,and can be dated back to October 2012.In March and April 2013,it began to spread to the neighboring provinces.The transmission speed up in August and September and affected more than ten geographic positions within 3 months.Conclusion Based on gene sequences and spatial geographic information,the transmission route of H7N9 virus was traced,which would support the avian influenza prevention and control as well as avian influenza virus tracing.


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