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.Informationized surveillance of central line-associated bloodstream infections in maintenance hemodialysis patients and risk factors
Ziqing GUO ; Menghan ZHAO ; Bing ZHANG ; Qi QI ; Yaoyao MA ; Jinping LIU ; Yiping MAO
Chinese Journal of Nosocomiology 2025;35(5):752-757
OBJECTIVE To explore the risk factors for central line-associated bloodstream infection(CLABSI)in the maintenance hemodialysis(MHD)patients based on the informatization surveillance system and establish and verify the risk prediction model so as to provide bases for early identification and prevention of CLABSI.METHODS A total of 300 MHD patients who were treated in hemodialysis center of the Affiliated Hospital of Xuzhou Medical University from Jan.2020 to Dec.2023 were recruited as the research subjects and were randomly divided into the training set group with 210 cases and the validation set group with 90 cases in a 7∶3 ratio.The risk factors for the CLABSI were analyzed,the prediction model was established and verified.The performance of the model was evaluated by the area under the curve(AUC)of receiver operating characteristic(ROC)curves and Hosmer-Lemeshow goodness of fit test.RESULTS Among the 300 MHD patients who were treated with central venous catheters,32 were diagnosed with CLABSI,and the incidence was 0.65 per 1,000 catheter days.Multivari-ate analysis showed that catheter indwelling time,repeated catheterization,previous history of catheter-related in-fection and diabetes mellitus were the risk factors for the CLABSI in the MHD patients(P<0.05).The model based on the logistic regression equation was established as follows:logit(P)=-5.661+0.024 × catheter in-dwelling duration(week)+2.037 × repeated catheterization+1.546 × previous history of catheter-related infec-tion+3.391× diabetes mellitus.ROC curve analysis showed that the AUC of the training set was 0.916(95%CI:0.837 to 0.994),with the sensitivity 87.00%,the specificity 86.63%,Youden index 0.736;the AUC of the vali-dation set was 0.797(95%CI:0.632 to 0.962),with the sensitivity 77.78%,the specificity 82.72%,the Youden index 0.605.The model showed excellent discrimination and calibration degree.CONCLUSION The logistic regres-sion equation that is established based on the 4 risk factors,catheter indwelling duration,repeated catheterization,previous history of catheter-related infection and diabetes mellitus,shows remarkable predictive efficiency,and it can provide evidence for clinical screening and prevention of CLABSI.
4.Informationized surveillance of central line-associated bloodstream infections in maintenance hemodialysis patients and risk factors
Ziqing GUO ; Menghan ZHAO ; Bing ZHANG ; Qi QI ; Yaoyao MA ; Jinping LIU ; Yiping MAO
Chinese Journal of Nosocomiology 2025;35(5):752-757
OBJECTIVE To explore the risk factors for central line-associated bloodstream infection(CLABSI)in the maintenance hemodialysis(MHD)patients based on the informatization surveillance system and establish and verify the risk prediction model so as to provide bases for early identification and prevention of CLABSI.METHODS A total of 300 MHD patients who were treated in hemodialysis center of the Affiliated Hospital of Xuzhou Medical University from Jan.2020 to Dec.2023 were recruited as the research subjects and were randomly divided into the training set group with 210 cases and the validation set group with 90 cases in a 7∶3 ratio.The risk factors for the CLABSI were analyzed,the prediction model was established and verified.The performance of the model was evaluated by the area under the curve(AUC)of receiver operating characteristic(ROC)curves and Hosmer-Lemeshow goodness of fit test.RESULTS Among the 300 MHD patients who were treated with central venous catheters,32 were diagnosed with CLABSI,and the incidence was 0.65 per 1,000 catheter days.Multivari-ate analysis showed that catheter indwelling time,repeated catheterization,previous history of catheter-related in-fection and diabetes mellitus were the risk factors for the CLABSI in the MHD patients(P<0.05).The model based on the logistic regression equation was established as follows:logit(P)=-5.661+0.024 × catheter in-dwelling duration(week)+2.037 × repeated catheterization+1.546 × previous history of catheter-related infec-tion+3.391× diabetes mellitus.ROC curve analysis showed that the AUC of the training set was 0.916(95%CI:0.837 to 0.994),with the sensitivity 87.00%,the specificity 86.63%,Youden index 0.736;the AUC of the vali-dation set was 0.797(95%CI:0.632 to 0.962),with the sensitivity 77.78%,the specificity 82.72%,the Youden index 0.605.The model showed excellent discrimination and calibration degree.CONCLUSION The logistic regres-sion equation that is established based on the 4 risk factors,catheter indwelling duration,repeated catheterization,previous history of catheter-related infection and diabetes mellitus,shows remarkable predictive efficiency,and it can provide evidence for clinical screening and prevention of CLABSI.
5.Effect of high-fat on NOX4-SIRT1 signaling pathway in vascular aging
Dandan SHI ; Meixia LIU ; Jiangang LIU ; Xiaochen GUO ; Ziqi NING ; Yaoyao ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(7):871-876
Objective To observe the alterations of protein expression of nicotinamide adenine di-nucleotide phosphatase oxidase 4-silent mating type information regulation 2 homolog 1(NOX4-SIRT1)signaling pathway in ApoE-/-mice and C57BL/6J mice induced by high-fat diet.Methods Twenty ApoE-/-mice and 40 C57BL/6J mice,aged of 10 weeks and half male and half female,were randomly divided into a NC group and a HFD group,with 10 mice in each group(ApoE-/-+NC and ApoE-/-+HFD groups,and C57+NC and C57+HFD groups).After 1 week of adaptive feed-ing period,each group was fed with their corresponding diet for subsequent 12 weeks,and then blood samples were collected from the anesthetized orbits and aortic arch tissues were harvested.HE staining and Masson staining were performed to examine the pathological morphology of the aortic arch tissues.The serum levels of TG,TC,HDL-C and LDL-C were measured using an auto-matic biochemical analyzer.The content of ox-LDLC was detected with ELISA,and the contents of ROS,GSH,GPX and NAD+were measured by colorimetry.The expression of SIRT1,p53,p21 and NOX4 was detected by Western blotting.Results Compared with the C57+NC group,the ApoE-/-+NC group showed significant lipid deposition,increased collagen fibers,elevated levels of TC,TG,HDLC,LDL-C,ox-LDL-C and ROS and increased p21 expression level,and obviously decreased contents of GSH,GPX and NAD+(P<0.05,P<0.01).Compared with the ApoE-/-+NC group,the ApoE-/-+HFD group showed larger plaque areas,lessened elastic fibers,more col-lagen fibers,increased levels of TC,HDL-C,LDL-C,ox-LDL-C and ROS,and p21 expression level(P<0.01),and declined expression of GSH,GPX,NAD+and NOX4[6.4±0.8 μmol/L vs 9.6±0.8 μmol/L,242.0±39.0 U/ml vs 362.7±11.1 U/ml,0.61±0.15 nmol/L vs 1.07±0.20 nmol/L,0.26±0.01 vs 0.32±0.03;P<0.05,P<0.01[.Conclusion High-fat diet may accelerate vascular aging by elevating lipid and oxidative stress levels,decreasing NAD+and NOX4 expression,ele-vating p21 expression,and thereby activating the NOX4-SIRT1 pathway.
6.Targeted surveillance on healthcare-associated infection in patients in emergency rescue room and observation room
Yaoyao MA ; Jinping LIU ; Qi QI ; Ziqing GUO ; Menghan ZHAO ; Yiping MAO
Chinese Journal of Infection Control 2025;24(10):1409-1415
Objective To explore the current situation of healthcare-associated infection(HAI)in patients in emergency rescue room and observation room,and analyze the causes.Methods Targeted surveillance was per-formed on patients in emergency rescue room and observation room of a tertiary first-class hospital in Xuzhou City from January 1 to December 31,2023 using prospective survey method.HAI,antimicrobial use,as well as invasive procedures and related infection rates were analyzed.Results The incidence of HAI in 540 patients was 0.19%(n=1),and the daily incidence of HAI was 0.54‰(1/1 841).The utilization rates of invasive ventilators,central ve-nous catheters,and indwelling urinary catheters were 6.79%(125/1 841),1.09%(20/1 841),and 2.93%(54/1 841),respectively.The incidences of ventilator-associated pneumonia,central line-associated bloodstream infec-tion,and catheter-associated urinary tract infection were 8.00‰(1/125),0(0/20),and 0(0/54),respectively.Pathogen detection rate before antimicrobial treatment was 99.22%(382/385).Conclusion The incidence of HAI in patients in emergency rescue room and observation room is low,the retention time of patients in rescue room is short,and pathogen detection of specimens before antimicrobial treatment is high.Patients in emergency rescue room and observation room are at high risk of HAI.It is necessary to carry out targeted surveillance on HAI to re-duce its incidence.
7.Current status of healthcare-associated infection management in 62 prima-ry medical institutions in Jiangsu Province
Menghan ZHAO ; Qi QI ; Ziqing GUO ; Jinping LIU ; Yaoyao MA ; Yiping MAO
Chinese Journal of Infection Control 2025;24(4):539-544
Objective To understand the application of healthcare-associated infection(HAI)quality control indi-cators and current status of HAI management in primary medical institutions in Jiangsu Province,and provide refe-rence and basis for primary medical institutions to improve HAI management quality and for health administrative departments to formulate HAI management relevant policies.Methods Data on HAI quality control indicators co-llected by Jiangsu Provincial Primary Healthcare Professional Quality Control Center from the first batch of 62 pri-mary sentinel medical institutions in the province were analyzed.Results of on-site inspections and assessments of 20 institutions were summarized and analyzed.Results From July 2023 to May 2024,a total of 145 814 inpatients were monitored,219 patients had 220 episodes of HAI.The incidence and case incidence of HAI were both 0.15%,and the main HAI site was upper respiratory tract(40.45%).The compliance rate and correct rate of hand hygiene were 81.34%(14.29%-100%)and 87.90%(18.46%-100%),respectively.The removal rate of surface pollu-tant from environmental objects was 77.24%(20.00%-100%),and the qualified rate of cleaning of device,appli-ances,and articles was 98.76%(10.00%-100%).The monitoring data records of quality control indicators in most primary healthcare institutions during on-site inspections didn't match the monthly data reported to the Jiangsu Provincial Primary Healthcare Professional Quality Control Center.Most healthcare workers in primary healthcare institutions lacked sufficient awareness and knowledge in infection prevention and control.Multiple HAI-related safety hazards existed in key departments of most primary medical institutions.Conclusion After nearly a year of continuous monitoring on HAI,the primary sentinel medical institutions have established their own data on the inci-dence of HAI.The compliance rate and correct rate of hand hygiene,as well as the removal rate of surface pollu-tants from environmental objects are still relatively low in some medical medical institutions,and there is much room for improvement.There is still a significant gap in terms of HAI prevention and control in some primary medical in-stitutions when referring to the standards.
8.Construction and usability evaluation of knowledge graph of healthcare-associated infection prevention and control course
Jinping LIU ; Yaoyao MA ; Bing ZHANG ; Menghan ZHAO ; Ziqing GUO ; Qi QI ; Yiping MAO
Chinese Journal of Infection Control 2025;24(5):666-673
Objective To construct a knowledge graph of healthcare-associated infection(HAI)prevention and control course,and evaluate its usability.Methods Based on the constructivist learning theory and the analyze-de-sign-develop-implement-evaluate(ADDIE)model,knowledge from various sources such as books,guidelines,and literature related to HAI prevention and control were integrated.The knowledge graph of HAI prevention and con-trol course were designed and constructed with the support of knowledge graph technology in Chaoxing Fanya plat-form.Thirty medical students were selected by convenience sampling method to try out the course knowledge graph.System usability scale and usage effect questionnaire were filled out to evaluate the usability of the knowledge graph.Results The knowledge graph of HAI prevention and control course contained 379 knowledge points asso-ciated with 520 test questions and 56 learning resources.After testing,the total score([70.50±12.20]points)was obtained for the usability of the knowledge graph.Among the four dimensions of the usage effect agreement ques-tionnaire,satisfaction,learning attitude,learning ability,and learning resource support accounted for 93.33%-96.67%,90.00%,93.33%-96.67%,and 83.33%-90.00%,respectively,with a high overall satisfaction rate.Conclusion The knowledge graph of HAI prevention and control course has good usability,which can realize students'personalized independent learning and improve their learning efficiency.
9.Targeted surveillance on healthcare-associated infection in patients in emergency rescue room and observation room
Yaoyao MA ; Jinping LIU ; Qi QI ; Ziqing GUO ; Menghan ZHAO ; Yiping MAO
Chinese Journal of Infection Control 2025;24(10):1409-1415
Objective To explore the current situation of healthcare-associated infection(HAI)in patients in emergency rescue room and observation room,and analyze the causes.Methods Targeted surveillance was per-formed on patients in emergency rescue room and observation room of a tertiary first-class hospital in Xuzhou City from January 1 to December 31,2023 using prospective survey method.HAI,antimicrobial use,as well as invasive procedures and related infection rates were analyzed.Results The incidence of HAI in 540 patients was 0.19%(n=1),and the daily incidence of HAI was 0.54‰(1/1 841).The utilization rates of invasive ventilators,central ve-nous catheters,and indwelling urinary catheters were 6.79%(125/1 841),1.09%(20/1 841),and 2.93%(54/1 841),respectively.The incidences of ventilator-associated pneumonia,central line-associated bloodstream infec-tion,and catheter-associated urinary tract infection were 8.00‰(1/125),0(0/20),and 0(0/54),respectively.Pathogen detection rate before antimicrobial treatment was 99.22%(382/385).Conclusion The incidence of HAI in patients in emergency rescue room and observation room is low,the retention time of patients in rescue room is short,and pathogen detection of specimens before antimicrobial treatment is high.Patients in emergency rescue room and observation room are at high risk of HAI.It is necessary to carry out targeted surveillance on HAI to re-duce its incidence.
10.Current status of healthcare-associated infection management in 62 prima-ry medical institutions in Jiangsu Province
Menghan ZHAO ; Qi QI ; Ziqing GUO ; Jinping LIU ; Yaoyao MA ; Yiping MAO
Chinese Journal of Infection Control 2025;24(4):539-544
Objective To understand the application of healthcare-associated infection(HAI)quality control indi-cators and current status of HAI management in primary medical institutions in Jiangsu Province,and provide refe-rence and basis for primary medical institutions to improve HAI management quality and for health administrative departments to formulate HAI management relevant policies.Methods Data on HAI quality control indicators co-llected by Jiangsu Provincial Primary Healthcare Professional Quality Control Center from the first batch of 62 pri-mary sentinel medical institutions in the province were analyzed.Results of on-site inspections and assessments of 20 institutions were summarized and analyzed.Results From July 2023 to May 2024,a total of 145 814 inpatients were monitored,219 patients had 220 episodes of HAI.The incidence and case incidence of HAI were both 0.15%,and the main HAI site was upper respiratory tract(40.45%).The compliance rate and correct rate of hand hygiene were 81.34%(14.29%-100%)and 87.90%(18.46%-100%),respectively.The removal rate of surface pollu-tant from environmental objects was 77.24%(20.00%-100%),and the qualified rate of cleaning of device,appli-ances,and articles was 98.76%(10.00%-100%).The monitoring data records of quality control indicators in most primary healthcare institutions during on-site inspections didn't match the monthly data reported to the Jiangsu Provincial Primary Healthcare Professional Quality Control Center.Most healthcare workers in primary healthcare institutions lacked sufficient awareness and knowledge in infection prevention and control.Multiple HAI-related safety hazards existed in key departments of most primary medical institutions.Conclusion After nearly a year of continuous monitoring on HAI,the primary sentinel medical institutions have established their own data on the inci-dence of HAI.The compliance rate and correct rate of hand hygiene,as well as the removal rate of surface pollu-tants from environmental objects are still relatively low in some medical medical institutions,and there is much room for improvement.There is still a significant gap in terms of HAI prevention and control in some primary medical in-stitutions when referring to the standards.

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