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.Correlation between depressive symptom and traditional Chinese medicine constitution among school aged children and adolescents
Chinese Journal of School Health 2025;46(9):1222-1225
Objective:
To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom.
Methods:
From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted.
Results:
The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05).
Conclusions
Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.
4.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.
5.Cost-Effectiveness of Inclisilan Injection in Patients with Atherosclerotic Cardiovascular Disease
Bing FENG ; Ning GAO ; Shengnan GAO ; Mengna NIU ; Shan GUO ; Guoqiang LIU
Herald of Medicine 2025;44(3):466-472
Objective To evaluate the cost-effectiveness of inclisiran injection treatment in patients with atherosclerotic heart disease(ASCVD)in China.Methods From the perspective of China's health system,according to the Markov model,patients with ASCVD were divided into inclisilan injection group and placebo group,and both groups were treated with convention-al lipid-lowering drugs.The study period was 25 years.The rate parameters,cost parameters,and effectiveness parameters were de-rived from the ORION-18 trial and other literature.Effects were expressed as quality-adjusted life-years(QALYs).The incremental cost-effectiveness ratio(ICER)was used to evaluate the economy of inclisilan injection.One-way sensitivity analysis and probabil-ity sensitivity analysis were used to verify the reliability of the results.Results The treatment effect of the inclisilan injection group was higher(10.02 QALYs),and the cost of the placebo group was lower(255 179 yuan).The ICER of the two groups was 137 850 yuan per QALY gained,and using 257 094 yuan per capita by 2022 as the threshold,the treatment would be economically advantageous.Sensitivity analysis supported this result.Conclusion At present,the additional use of inclisilan injection can get a better treatment effect,and it has economic advantages under the threshold of three times GDP per capita in China.
6.A comparison and prediction study of wide-field swept-source optical coher-ence tomography angiography in identifying non-perfusion areas in diabetic retinopathy
Chuyun GUO ; Yue HAN ; Li CHEN ; Yi LIU ; Hongzhuang CHENG ; Xinru NING ; Yadan SHEN ; Ruolan LING ; Jie ZHONG ; Jie LI
Recent Advances in Ophthalmology 2025;45(3):211-215
Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40%,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56%in the superotemporal quad-rant,58.35%in the inferotemporal quadrant,45.50%in the superonasal quadrant,and 43.17%in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71%of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00%in the superonasal quadrant and 78.41%in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.
7.Efficacy and safety of bridging therapy versus direct thrombectomy in acute basilar artery occlusive stroke within 4.5 hours of onset
Rongyi LIU ; Changming WEN ; Jun SUN ; Ning WANG ; Zaixing ZHANG ; Yanjun GUO ; Yuanzhan GUO ; Haocun ZHENG
Chinese Journal of Cerebrovascular Diseases 2025;22(3):145-156
Objective To compare the efficacy and safety of bridging therapy and direct thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion within 4.5 h.Methods Retrospective consecutive patients with acute basilar artery occlusion stroke within 4.5 h of onset admitted to five centers from January 2018 to August 2024 were included and divided into a bridging therapy(intravenous thrombolysis with alteplase given prior to emergency endovascular treatment)group and a direct thrombectomy group according to the treatment modality.Baseline and clinical data were collected from patients,including age,sex,systolic and diastolic blood pressure on admission,past history(including history of hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,hyperlipidemia,and history of stroke),history of smoking,pre-morbid modified Rankin scale(mRS)scores,National Institutes of Health stroke scale(NIHSS)score on admission,posterior circulation Alberta stroke program early CT score on admission,basilar artery CT angiography score,history of pre-procedural antiplatelet aggregation medications,history of pre-procedural anticoagulant medications,choice of arterial puncture access(via femoral or radial artery),site of vascular occlusion(proximal basilar artery,mid-basilar artery,distal basilar artery),trial of Org 10172 in acute stroke treatment(TOAST)classification,American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral circulation classification,time from onset to admission,time from admission to puncture,time from puncture to revascularization,time from onset to revascularisation,type of embolisation procedure(stenting,aspiration,and combined),immediate post-procedure extended thrombolysis in cerebral infarction(eTICI)classification,and intra-procedural related complications(arterial entrapment,distal occlusion and arterial perforation).The main efficacy indicators(good prognosis[mRS score 0-3 90 d postoperatively],death[mRS score 6 90 d postoperatively],and good recanalisation[eTICI grade ≥2b50]within the immediate postoperative period)and safety indicators(incidence of symptomatic intracranial haemorrhage[sICH]within 7 days post-procedure)were compared between the two groups.The two groups were matched 1∶1 using propensity score matching(PSM)to compare differences in effectiveness and safety indices before and after PSM.Variables with P<0.05 in the baseline and clinical data comparison between the two groups were included in multifactorial Logistic regression analysis for correction,the differences in safety and efficacy between the two groups were compared before and after correction.Results A total of 206 patients with acute ischemic stroke caused by basilar artery occlusion within 4.5 h of onset were included,comprising 151 males and 55 females.The age ranged from 26 to 93 years old,with an average of(65±13)years old.Among them,101 patients(49.0%)were in the bridging therapy group and 105(51.0%)in the direct thrombectomy group.After 1∶1 PSM,each group consisted of 69 patients.(1)The differences in the proportion of patients with atrial fibrillation between the bridging therapy group and the direct thrombectomy group(16.8%[17/101]vs.28.6%[30/105]),the distribution of pre-morbid mRS scores,and the distribution of TOAST subtypes were statistically significant(all P<0.05);the differences in the residual baseline and clinical data of the two groups were not statistically significant(all P>0.05).After 1∶1 PSM,the differences in all baseline and clinical data between the two groups were not statistically significant(all P>0.05).(2)No statistically significant differences were observed between the bridging therapy group and direct thrombectomy group in the good prognosis rate at 90 d postoperatively,morbidity and mortality rates at 90 d postoperatively,or good revascularization rate in the immediate postoperative period(all P>0.05).However,the risk of sICH at 7 d postoperatively was higher in the bridging therapy group(9.5%[10/105]vs.19.8%[20/101];OR,2.346,95%CI 1.038-5.299,P=0.037).After correcting for variables with statistically significant differences in baseline and clinical data between the direct thrombectomy group and bridging therapy groups(atrial fibrillation,pre-onset mRS score,and TOAST classification)using a multifactorial Logistic regression model,the results showed no statistically significant differences in the effectiveness and safety metrics between the two groups(all P>0.05).(3)The results after 1∶1 PSM showed that the bridging therapy group had a higher risk of sICH(11.6%[8/69]vs.26.1%[18/69];OR,2.691,95%CI 1.081-6.700,P=0.033).No statistically significant differences were observed between the two groups in terms of good prognosis rate at 90 d postoperatively,disease-related mortality rate at 90 d postoperatively,or rate of good revascularization in the immediate postoperative period(all P>0.05).Conclusions In patients with acute basilar artery occlusion stroke within 4.5 h of onset,the effectiveness of bridging therapy and direct thrombectomy was similar,but the incidence of sICH was higher with bridging therapy.The results of this study still need further validation through prospective studies with larger sample sizes.
8.Methods for enhancing medical equipment management in rehabilitation and recuperation institutions
Shu-cheng HE ; Ji-liang LIU ; Zheng LIU ; Jing LI ; Ning GUO
Chinese Medical Equipment Journal 2025;46(10):91-96
The current situation of the medical equipment allocation was introduced in some rehabilitation and recuperation institution.The problems of the medical equipment were analyzed in terms of allocation planning,demand plan submission,use management,risk management and quality control,and some measures for enhancing medical equipment management of rehabilitation and recuperation institutions were put forward in unit-based allocation planning,precision planning management,standardized use management,all-element risk management and systemic quality control.References were provided for improving medical equipment application and management in similar rehabilitation and recuperation institutions.[Chinese Medical Equipment Journal,2025,46(10):91-96]
9.Development of sandwich ELISA for detection of soluble advanced oxidative protein products
Xiaorui HOU ; Ping ZHU ; Yonghui GUO ; Ning FU ; Beiyi LIU
Chinese Journal of Immunology 2025;41(5):1208-1214
Objective:To develop a double-antibody sandwich ELISA for detecting soluble advanced oxidation protein products(AOPPs).Methods:BALB/c mice were immunized with sodium hypochlorite-oxidized mouse albumin to generate AOPPs-specific monoclonal antibodies(mAbs).Specificity of the mAbs was assessed using indirect ELISA and Western blot.Competitive ELISA was employed to determine if the epitope recognized by newly prepared mAb was consistent with that recognized by mAb 3F2,which developed in our previous work.The sandwich ELISA was then established,and its specificity and sensitivity were compared with the chloramine-T method,the repeatability of double-mAb sandwich ELISA was verified.Results:A mAb AP-4C5 with specific AOPPs recognition was obtained,two sandwich ELISA were developed for the specific detection of soluble AOPPs.Double-mAb sandwich ELISA,using mAb 3F2 as the capture antibody and mAb AP-4C5 as the detection antibody,detected AOPPs in range of 0.25~2 μg/ml(R2=0.991 80).PcAb-mAb sandwich ELISA,using goat anti-HSA polyclonal antibody as the capture antibody and AP-4C5 as detection antibody,detected AOPPs in range of 1.5~25 μg/ml(R2=0.968 75).The double-mAb sandwich ELISA was found to be more sensitive and specific compared to chloramine-T method.Double-mAb sandwich ELISA has good reproducibility(intra-assay CV:3.23%~4.51%,inter-assay CV:3.08%~5.29%).Conclusion:Two kinds of sandwich ELISA for detecting soluble AOPPs have been estab-lished,which hold promise for the detection of clinical samples and understanding of the pathogenic mechanisms of AOPPs.
10.Predictive value of serum AMH for micro-TESE outcomes in patients with non-mosaic Klinefelter syndrome
Hang XIN ; Jinhao LIU ; Wenbin NIU ; Shanjun DAI ; Yu LIU ; Yudong GUAN ; Ning XU ; Yihong GUO
Chinese Journal of Reproduction and Contraception 2025;45(4):372-379
Objective:To investigate the predictive value of anti-Müllerian hormone (AMH) on the outcome of microscopic testicular sperm extraction (micro-TESE) in patients with non-mosaic Klinefelter syndrome (KS) of the clinical data and to identify effective predictors for successful micro-TESE.Methods:A retrospective case-control study was conducted on the clinical data of 118 non-mosaic KS patients treated at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University between May 2018 and September 2023. Patients were divided into two groups based on whether sperm were successfully retrieved via micro-TESE: the sperm retrieved group ( n=45) and the no sperm retrieved group ( n=73). Differences between the two groups were compared, and multivariate logistic regression analysis was used to identify factors influencing sperm retrieval. Changes in testicular volume and sex hormone levels before and after surgery were also assessed. Results:The sperm retrieval rate was 38.1% (45/118). Patients in the sperm retrieved group were significantly younger [(26.93±3.80) years] than those in the no sperm retrieved group [(28.27±3.92) years, P=0.029], and the AMH level was significantly higher [0.44 (0.18, 1.13) μg/L] than that in the no sperm retrieved group [0.10 (0.03, 0.22) μg/L, P<0.001]. AMH was identified as an independent predictor of micro-TESE outcome in non-mosaic KS patients ( OR=7.867, 95% CI: 2.727-27.242, P=0.001). The area under the receiver operating characteristic curve was 0.802 (95% CI: 0.722-0.883), and the optimal reference threshold for AMH was ≥0.265 μg/L. Postoperatively, testosterone levels decreased significantly by a median of 0.27 μg/L ( P=0.019), while luteinizing hormone levels increased by a median of 2.08 U/L ( P=0.049), with a more significant decline in testosterone levels observed in the no sperm retrieved group by a median of 0.29 μg/L ( P=0.022). Conclusion:AMH can predict successful micro-TESE in non-mosaic KS patients, with higher AMH levels indicating a higher likelihood of success.


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