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.Value of healthcare failure mode and effect analysis mode combined with enhanced management of link quality in centralized processing of rigid endoscopic instruments
Fei NING ; Qiang CHEN ; Lei GUO ; Yang ZHANG ; Yuanyuan XIANG ; Fang LIU ; Cai SUN
Chinese Journal of Nosocomiology 2025;35(10):1567-1571
OBJECTIVE To explore the value of healthcare failure mode and effect analysis mode(HFMEA)com-bined with enhanced management of link quality in centralized processing of rigid endoscopic instruments.METHODS Totally 80 pieces of rigid endoscopic instruments that were recycled by the endoscopy room of otolar-yngology department of The First Medical Center of PLA General Hospital from Jan.2022 to Dec.2022 were as-signed as the control group,and 70 pieces of rigid endoscopic instruments that were recycled under the HFMEA model combined with enhanced management of link quality from Jan.2023 to Dec.2023 were assigned as the ex-perimental group.The effect of the management and the qualified rate of instruments were compared between the two groups of instruments,compare the satisfaction under the different intervention modes.RESULTS The scores of instrument disassembly and assembly,cleaning procedures,cleaning quality,environmental management and packaging quality were higher in the experimental group than in the control group(P<0.05).The unqualified rate of instruments of the experimental group was 10.00%,lower than 23.75%of the control group(x2=4.926,P=0.026).The staff's satisfaction with the work of the experimental group was 91.67%,higher than 66.67%of the control group(Z=2.026,P=0.043).CONCLUSION For the centralized management of rigid endoscopic in-struments,the implementation of the enhanced management of link quality under the HFMEA mode can effective-ly improve the effect of management of the instruments and reduce the unqualified rate of recycled instruments,demonstrating a positive effect on raising the staff's satisfaction with the recycle process of instruments.
4.Clinical features and short-medium term follow-up of children with severe multisystem inflammatory syndrome
Yue LIU ; Jian ZHANG ; Biru LI ; Botao NING ; Fang ZHANG ; Teng TENG ; Hong REN
Chinese Pediatric Emergency Medicine 2025;32(1):38-43
Objective:To analyze and summarize the clinical features and short-medium term follow-up results of children with multisystem inflammatory syndrome(MIS-C)following coronavirus infection.Methods:The data of six children with MIS-C admitted to the Intensive Care Unit of Shanghai Children's Medical Center from January to March 2023 were retrospectively analyzed.Results:All six cases were in shock,requiring vasoactive drugs,and one case required invasive mechanical ventilation.All the six patients had multiple organ function injury and increased inflammation indicators.After admission,they received organ support,glucocorticoids and gamma globulin treatment.Two patients were treated with biological agents.Both organ function and inflammation indicators showed significantly improvement after therapy.Six patients had mild coronary artery widening.All patients had good prognosis following short-medium term follow-up.Conclusion:Children with severe MIS-C may suffer life-threatening hemodynamic instability.Timely assessment,active anti-inflammatory and organ support therapy can obtain favorable prognosis.
5.Effects of circadian rhythm on anxiety,depression,and cognitive behavior in mice with chronic restraint stress
Meng QIANG ; Ning JIANG ; Hong HUANG ; Yiwen ZHANG ; Fang CHEN ; Zhaohui LI ; Xinmin LIU ; Guanghua LYU
Chinese Journal of Comparative Medicine 2025;35(2):45-57
Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P<0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P<0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P<0.05)and the daytime restraint group(P<0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P<0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P<0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P<0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P<0.01,P<0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P<0.05,P<0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.
6.Systematic review of a body image assessment tool for burn patients
Ning LIU ; Jingling LI ; Shunli ZUO ; Xiuyuan ZHU ; Yiping FANG ; Lihong QIU
Chinese Journal of Nursing 2025;60(4):478-486
Objective The measurement characteristics of body image specificity evaluation tools for burn patients were systematically evaluated,aims to provide reference for selecting appropriate assessment tools.Methods CNKI,Wanfang data knowledge service platform,VIP database,China Biomedical Literature Service system,PubMed,Embase,Web of Science,PsycINFO and CINAHL were searched by computer to collect and evaluate the measurement characteristics of burn patients'body image specificity evaluation tools from the establishment of the database to April 15,2024.There were 2 researchers who independently reviewed the collected literature,looked for the full text and extracted information.At the same time,the methodological quality and measurement performance of such assessment tools were systematically evaluated under the guidance of consensus-based standards for the selection of health measurement instrument(COSMIN)guidelines.Finally,the quality and strength were rated to form a recommendation.Results A total of 6 studies were included,including 3 evaluation tools for body image specificity of burn patients,namely the Body Image Quality of Life Inventory into Brazilian Portuguese(BIQLI-BP),Satisfaction with Appearance Scale(SWAP),and the Derriford Appearance Scale 59(DAS59).In the development of PROMs,the overall quality of BIQLI-BP,SWAP and DAS59 is"doubtful".In terms of content validity,the methodological quality of BIQLI-BP,SWAP and DAS59 was evaluated as"doubtful".In terms of construct validity,the methodological quality of SWAP and DAS59 was evaluated as"good"and"very good"respectively,while the methodological quality of BIQLI-BP was"inadequate".In terms of internal consistency,the methodological quality of BIQLI-BP,SWAP and DAS59 was"very good".In terms of stability,the BIQLI-BP and DAS59 were"unreported",and the methodological quality evaluation of the SWAP was"doubtful".In terms of criterion validity,the BIQLI-BP and DAS59 scales were"unreported",and the methodological quality evaluation of the SWAP scale was"inadequate".In terms of measurement errors,the BIQLI-BP and DAS59 scales were"unreported",and the methodological quality evaluation of the SWAP scale was"doubtful".In the aspect of hypothesis test,except that the DAS59 scale is"unreported",the methodological quality of BIQLI-BP scale is"very good"and the evaluation of SWAP scale is"doubtful".Conclusion Among the existing body image specificity evaluation tools for burn patients,the SWAP has good measurement performance and it can be recommended for the time being.The number of specific evaluation tools for body image of burn patients in China is relatively insufficient,and more localization studies should be carried out in the future.
7.Value of healthcare failure mode and effect analysis mode combined with enhanced management of link quality in centralized processing of rigid endoscopic instruments
Fei NING ; Qiang CHEN ; Lei GUO ; Yang ZHANG ; Yuanyuan XIANG ; Fang LIU ; Cai SUN
Chinese Journal of Nosocomiology 2025;35(10):1567-1571
OBJECTIVE To explore the value of healthcare failure mode and effect analysis mode(HFMEA)com-bined with enhanced management of link quality in centralized processing of rigid endoscopic instruments.METHODS Totally 80 pieces of rigid endoscopic instruments that were recycled by the endoscopy room of otolar-yngology department of The First Medical Center of PLA General Hospital from Jan.2022 to Dec.2022 were as-signed as the control group,and 70 pieces of rigid endoscopic instruments that were recycled under the HFMEA model combined with enhanced management of link quality from Jan.2023 to Dec.2023 were assigned as the ex-perimental group.The effect of the management and the qualified rate of instruments were compared between the two groups of instruments,compare the satisfaction under the different intervention modes.RESULTS The scores of instrument disassembly and assembly,cleaning procedures,cleaning quality,environmental management and packaging quality were higher in the experimental group than in the control group(P<0.05).The unqualified rate of instruments of the experimental group was 10.00%,lower than 23.75%of the control group(x2=4.926,P=0.026).The staff's satisfaction with the work of the experimental group was 91.67%,higher than 66.67%of the control group(Z=2.026,P=0.043).CONCLUSION For the centralized management of rigid endoscopic in-struments,the implementation of the enhanced management of link quality under the HFMEA mode can effective-ly improve the effect of management of the instruments and reduce the unqualified rate of recycled instruments,demonstrating a positive effect on raising the staff's satisfaction with the recycle process of instruments.
8.The Mechanism of Necroptosis in Cancer Therapy
Yan-Ping NING ; Liu-Yan CHEN ; Su-Fang ZHOU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(11):1622-1632
Cell death is classified into programmed cell death(PCD)and non-programmed cell death(NCD).Necroptosis is a form of PCD that does not rely on caspases and is regulated by four signaling pathways:receptor-interacting protein kinase 1/3(RIPK1-RIPK3),TIR-domain-containing adapter-in-ducing interferon-β(TRIF)-RIPK3,Z-DNA binding protein 1(ZBP1)-RIPK3,and type Ⅰ/Ⅱ interferon receptors(IFNRs).These pathways interact to regulate the activity of core molecules such as RIPK1,RIPK3,and mixed lineage kinase domain-like protein(MLKL),thereby determining the occurrence of necroptosis.The dysregulation of these pathways can lead to the development of various diseases,inclu-ding cancer.Necroptosis not only inhibits tumor occurrence and progression by promoting tumor cell death,but also creates a tumor microenvironment(TME)conducive to tumor cell growth through its pro-inflammatory properties,thereby promoting tumor growth and metastasis.Therefore,the dual role of nec-roptosis in cancer makes it an important research direction in tumor treatment.This article reviews the key signaling pathways of necroptosis,explores its interactions with other cell death pathways such as cell survival,apoptosis,and pyroptosis.Meanwhile,it analyzes the dual regulatory mechanisms of necropto-sis in cancer progression and discusses the issue of overcoming tumor treatment resistance by modulating necroptosis.It further explores its potential therapeutic targets and application prospects,aiming to pro-vide new intervention strategies and theoretical basis for cancer treatment.
9.Establishment of an animal model of comorbid anxiety and depression induced by sleep interruption stress based on behavioral experiments
Yongzhi ZHAO ; Yiwen ZHANG ; Yanqin LUO ; Fang CHEN ; Yanfei XU ; Ruile PAN ; Qi CHANG ; Mengchao LIU ; Qinghu HE ; Ning JIANG ; Xinmin LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(5):695-703
Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4~5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P<0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P<0.05)and a significant increase in the number of marbles buried(P<0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P<0.05),a significant decrease in the number of crossings in the light-dark box(P<0.05),and a significant increase in immobility time in the forced-swim test(P<0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.
10.Clinical features and short-medium term follow-up of children with severe multisystem inflammatory syndrome
Yue LIU ; Jian ZHANG ; Biru LI ; Botao NING ; Fang ZHANG ; Teng TENG ; Hong REN
Chinese Pediatric Emergency Medicine 2025;32(1):38-43
Objective:To analyze and summarize the clinical features and short-medium term follow-up results of children with multisystem inflammatory syndrome(MIS-C)following coronavirus infection.Methods:The data of six children with MIS-C admitted to the Intensive Care Unit of Shanghai Children's Medical Center from January to March 2023 were retrospectively analyzed.Results:All six cases were in shock,requiring vasoactive drugs,and one case required invasive mechanical ventilation.All the six patients had multiple organ function injury and increased inflammation indicators.After admission,they received organ support,glucocorticoids and gamma globulin treatment.Two patients were treated with biological agents.Both organ function and inflammation indicators showed significantly improvement after therapy.Six patients had mild coronary artery widening.All patients had good prognosis following short-medium term follow-up.Conclusion:Children with severe MIS-C may suffer life-threatening hemodynamic instability.Timely assessment,active anti-inflammatory and organ support therapy can obtain favorable prognosis.

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