1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Yinqiao Powder affects macrophage polarization-mediated herpes simplex keratitis through the cGAS-STING-IRF3 molecular pathway
Ning YAO ; Rongli ZHAO ; Xuemei YANG ; Yuhuan LIU ; Yaqin DING ; Yan DAI
International Eye Science 2025;25(8):1227-1233
AIM: To investigate the specific molecular mechanism of Yinqiao Powder in affecting macrophage polarization in herpes simplex keratitis(HSK)through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)molecular pathway.METHODS:Human corneal epithelial cells(HCE-T)were divided into control, HSK, and HSK + Yinqiao Powder groups. M0 macrophages were grouped as Ctrl, HSV-1, HSV-1+oe-cGAS, HSV-1+Yinqiao Powder, and HSV-1+oe-cGAS+Yinqiao Powder. Conditional medium(CM)from each group of M0 macrophages was collected to intervene in HCE-T cells and divided into Ctrl-CM, HSV-1-CM, HSV-1+oe-cGAS-CM, and HSV-1+Yinqiao Powder-CM groups. Cell viability was detected by MTT assay, and apoptosis was detected by TUNEL assay. ELISA was used to detect the concentrations of Arg-1 and iNOS in cell supernatants, and Western blotting was used to detect the relative protein expressions of cGAS, STING, and IRF3. Balb/c mice were divided into control, model, and drug groups. The model and drug groups were inoculated with HSV-1 on the cornea of Balb/c mice using the corneal scratch method to construct an HSK mouse model, and the drug group was treated with Yinqiao Powder. The incidence and mortality of the three groups were compared on days 1, 3, 5, 7, and 14 after modeling.RESULTS:Compared with the control group, the HCE-T cell viability in the HSK group was decreased but apoptosis was increased, which was reversed by Yinqiao Powder intervention. Compared with the Ctrl group, the Arg-1 concentration in the cell supernatant of the HSV-1 group was decreased, the iNOS concentration was increased, and the protein expressions of cGAS, STING, and IRF3 were decreased. Compared with the HSV-1 group, the Arg-1 concentration was increased, the iNOS concentration was decreased, and the protein expressions of cGAS, STING, and IRF3 were enhanced in the HSV-1+oe-cGAS group and the HSV-1+Yinqiao Powder group, and the same results were obtained in the HSV-1+oe-cGAS+Yinqiao Powder group. Compared with the Ctrl-CM group, the HCE-T cell viability was decreased and apoptosis was increased in the HSV-1-CM group, which was reversed by overexpressing cGAS in macrophages or intervening with Yinqiao Powder. In vivo experiments found that Yinqiao Powder intervention could improve the pathological progression of keratitis.CONCLUSION:Yinqiao Powder inhibits M1 polarization of macrophages through the cGAS-STING-IRF3 molecular pathway, thereby delaying the progression of HSK.
4.MR MAGiC sequence based on deep learning reconstruction for localizing epileptogenic focus of intractable epilepsy
Jingjuan WANG ; Huijuan XU ; Yaqin HOU ; Sudeep KHAREL ; Chenyang YAO ; Jie HU ; Siqi ZHANG ; Jie LU
Chinese Journal of Medical Imaging Technology 2025;41(9):1468-1472
Objective To explore the application value of MR MAGiC sequence reconstructed based on deep learning reconstruction(DLR)for localizing epileptogenic focus of intractable epilepsy.Methods Fifty intractable epilepsy patients(epilepsy group)and 20 healthy controls(control group)were retrospectively collected.Brain MR MAGiC sequence was scanned,then traditional reconstruction(inverse Fourier transform)and DLR algorithm were performed to obtain MAGiC and MAGiC DLR images,respectively.The corresponding quantitative parameter maps were generated after post-processing,including T1 mapping,T2 mapping and proton density(PD)mapping.The subjective scores of noise,artifacts,structural clarity and overall quality were compared between two kinds of quantitative parameter images.The asymmetry index(AI)of quantitative parameters(T1,T2 and PD values)between the affected side and the contralateral side in epilepsy group,the contralateral side or the suspected epileptogenic focus in epilepsy group and HC group were calculated.Then epileptogenic focus were localized based on performance of MAGiC and MAGiC DLR corresponding quantitative parameter maps combining obtained AI of quantitative parameter values.According to surgical results,follow-up review,electroencephalogram or PET results,the accuracy of MAGiC and MAGiC DLR images for localizing epileptogenic focus was calculated.Results Compared with MAGiC quantitative parametric maps,noise of MAGiC DLR quantitative parametric maps reduced,while subjective scores of structure clarity and overall quality improved(all P<0.05).The accuracy of MAGiC and MAGiC DLR images for localizing epileptogenic focus was 82.00%(41/50)and 88.00%(44/50),respectively.Conclusion MR MAGiC sequence based on DLR was beneficial for improving accuracy of localizing epileptogenic focus in intractable epilepsy.
5.Construction of a nomogram prediction model for coronary in-stent restenosis based on LASSO-machine learning combined with CT-FFR
Wusiman GULINIGAER ; Weiping JIANG ; Yaqin TENG ; Jihong YU ; Zhenxiang WANG ; Liang YAO
Chinese Journal of Arteriosclerosis 2025;33(11):971-980
Aim Based on coronary CT-fractional flow reserve(CT-FFR)combined with machine learning methods,a nomogram prediction model for coronary in-stent restenosis(ISR)was developed to assess the risk of ISR.Methods Retrospective analysis was performed on patients who underwent re-examination after PCI at our hospital from January 2022 to January 2025.According to the exclusion criteria,a total of 210 patients were enrolled,including 100 cases of ISR and 110 cases of non-ISR.The dataset was randomly divided into training and test sets at a 7∶3 ratio.Af-ter univariate analysis to screen potential predictors,LASSO regression was applied to identify feature variables with non-ze-ro coefficients.Subsequently,three machine learning(ML)algorithms including random forest(RF),support vector machine(SVM),and extreme gradient boosting(XGB)were used to rank the importance of the significant factors.The intersection of the top 10 variables from each algorithm was used as input for bidirectional stepwise multivariate Logistic re-gression.An ISR risk score was then constructed and visualized using a nomogram.Results A total of 14 predictive factors were identified through LASSO regression,including diastolic blood pressure,C-reactive protein,triglycerides(TG),N-terminal pro-brain natriuretic peptide(NT-proBNP),low density lipoprotein cholesterol(LDLC),minimum stent diameter<3 mm,systolic blood pressure,△CT-FFR,CT-FFR,interleukin-6(IL-6),body mass index,glycosylated hemoglobin(HbA1c),history of hypertension,and high density lipoprotein cholesterol(HDLC).Following stepwise screening using three ML algorithms and Logistic regression,six independent risk factors for ISR were identified:elevated△CT-FFR,IL-6,NT-proBNP,TG and CT-FFR values,and minimum stent diameter<3 mm.The area under the curve for the training set and test set were 0.995(95%CI:0.989~1.000)and 0.965(95%CI:0.927~1.000),respectively.Decision curve analysis demonstrated high net benefit across threshold probabilities of 0~1.00 in the training set and 0~0.92 in the test set.The nomogram integrating these six predictors exhibited high accuracy and clinical utility.Con-clusion The ISR nomogram prediction model based on LASSO-ML combined with CT-FFR technology has high accuracy and clinical utility for ISR.
6.MR MAGiC sequence based on deep learning reconstruction for localizing epileptogenic focus of intractable epilepsy
Jingjuan WANG ; Huijuan XU ; Yaqin HOU ; Sudeep KHAREL ; Chenyang YAO ; Jie HU ; Siqi ZHANG ; Jie LU
Chinese Journal of Medical Imaging Technology 2025;41(9):1468-1472
Objective To explore the application value of MR MAGiC sequence reconstructed based on deep learning reconstruction(DLR)for localizing epileptogenic focus of intractable epilepsy.Methods Fifty intractable epilepsy patients(epilepsy group)and 20 healthy controls(control group)were retrospectively collected.Brain MR MAGiC sequence was scanned,then traditional reconstruction(inverse Fourier transform)and DLR algorithm were performed to obtain MAGiC and MAGiC DLR images,respectively.The corresponding quantitative parameter maps were generated after post-processing,including T1 mapping,T2 mapping and proton density(PD)mapping.The subjective scores of noise,artifacts,structural clarity and overall quality were compared between two kinds of quantitative parameter images.The asymmetry index(AI)of quantitative parameters(T1,T2 and PD values)between the affected side and the contralateral side in epilepsy group,the contralateral side or the suspected epileptogenic focus in epilepsy group and HC group were calculated.Then epileptogenic focus were localized based on performance of MAGiC and MAGiC DLR corresponding quantitative parameter maps combining obtained AI of quantitative parameter values.According to surgical results,follow-up review,electroencephalogram or PET results,the accuracy of MAGiC and MAGiC DLR images for localizing epileptogenic focus was calculated.Results Compared with MAGiC quantitative parametric maps,noise of MAGiC DLR quantitative parametric maps reduced,while subjective scores of structure clarity and overall quality improved(all P<0.05).The accuracy of MAGiC and MAGiC DLR images for localizing epileptogenic focus was 82.00%(41/50)and 88.00%(44/50),respectively.Conclusion MR MAGiC sequence based on DLR was beneficial for improving accuracy of localizing epileptogenic focus in intractable epilepsy.
7.Construction of a nomogram prediction model for coronary in-stent restenosis based on LASSO-machine learning combined with CT-FFR
Wusiman GULINIGAER ; Weiping JIANG ; Yaqin TENG ; Jihong YU ; Zhenxiang WANG ; Liang YAO
Chinese Journal of Arteriosclerosis 2025;33(11):971-980
Aim Based on coronary CT-fractional flow reserve(CT-FFR)combined with machine learning methods,a nomogram prediction model for coronary in-stent restenosis(ISR)was developed to assess the risk of ISR.Methods Retrospective analysis was performed on patients who underwent re-examination after PCI at our hospital from January 2022 to January 2025.According to the exclusion criteria,a total of 210 patients were enrolled,including 100 cases of ISR and 110 cases of non-ISR.The dataset was randomly divided into training and test sets at a 7∶3 ratio.Af-ter univariate analysis to screen potential predictors,LASSO regression was applied to identify feature variables with non-ze-ro coefficients.Subsequently,three machine learning(ML)algorithms including random forest(RF),support vector machine(SVM),and extreme gradient boosting(XGB)were used to rank the importance of the significant factors.The intersection of the top 10 variables from each algorithm was used as input for bidirectional stepwise multivariate Logistic re-gression.An ISR risk score was then constructed and visualized using a nomogram.Results A total of 14 predictive factors were identified through LASSO regression,including diastolic blood pressure,C-reactive protein,triglycerides(TG),N-terminal pro-brain natriuretic peptide(NT-proBNP),low density lipoprotein cholesterol(LDLC),minimum stent diameter<3 mm,systolic blood pressure,△CT-FFR,CT-FFR,interleukin-6(IL-6),body mass index,glycosylated hemoglobin(HbA1c),history of hypertension,and high density lipoprotein cholesterol(HDLC).Following stepwise screening using three ML algorithms and Logistic regression,six independent risk factors for ISR were identified:elevated△CT-FFR,IL-6,NT-proBNP,TG and CT-FFR values,and minimum stent diameter<3 mm.The area under the curve for the training set and test set were 0.995(95%CI:0.989~1.000)and 0.965(95%CI:0.927~1.000),respectively.Decision curve analysis demonstrated high net benefit across threshold probabilities of 0~1.00 in the training set and 0~0.92 in the test set.The nomogram integrating these six predictors exhibited high accuracy and clinical utility.Con-clusion The ISR nomogram prediction model based on LASSO-ML combined with CT-FFR technology has high accuracy and clinical utility for ISR.
8.The application of financial supervision in performance evaluation of public hospitals
Shengnan YAO ; Zeyun ZHANG ; Yaqin ZHU
Modern Hospital 2024;24(12):1879-1881,1886
In order to explore solutions to the problems of numerical quality,in-process supervision,and utilization of assessment results in performance evaluation of public hospitals,this article explores the application mechanism of financial su-pervision in performance evaluation of public hospitals.By analyzing the problems existing in current performance evaluation,the necessity of introducing financial supervision is proposed,and the application strategies and specific practices of financial supervi-sion in performance evaluation are elaborated in detail,in order to provide reference for improving the performance evaluation work of public hospitals.
9.Clinical characteristics and prognostic analysis of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia
Dun JIANXIN ; Zhang AI ; Wang YAQIN ; Wang YAO ; Liu AIGUO ; Hu QUN
Chinese Journal of Clinical Oncology 2024;51(11):547-551
Objective:To analyze the clinical characteristics and risk factors of asparaginase-associated pancreatitis(AAP)in children with acute lymphoblastic leukemia(ALL),and to investigate the impact of AAP on their prognosis following re-exposure to asparaginase(ASP).Methods:Clinical children data with ALL at Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology between January 2015 and June 2020 were collected to analyze the clinical features of AAP.Logistic regression was used to identify risk factors for AAP.Prognostic analysis was performed using the Log-rank test and Kaplan-Meier survival curves.Results:Overall,252 children with ALL were included,among whom 23(9.1%)developed AAP.Most AAP cases(82.6%)occurred during remission induction,with a medi-an time from the last ASP to AAP of 12 d.Elevated total cholesterol(≥3.5 mmol/L)at initial diagnosis was identified as an independent risk factor.Six children(26.1%)were re-exposed to ASP,leading to recurrent pancreatitis in 3 cases.The 5-year overall survival(OS)was signific-antly lower in the AAP group(78.3%±8.6%)compared to the non-AAP group(90.3%±2.2%)(P<0.05).Similarly,children who discontinued ASP due to AAP had a 5-year OS of 77.8%±9.8%,significantly lower than the control group(90.1%±2.1%).Conclusions:AAP typically oc-curred within 12 d of the last ASP administration and was associated with poorer 5-year OS.Re-exposure to ASP posed a risk of recurrent AAP;however,completing the ASP chemotherapy regimen may be crucial for improving prognosis.
10.Construction and application of a spinal cord injury rehabilitation care platform based on patient portrait
Yaqin DAI ; Ting SHAO ; Lifeng YAO ; Fei HU ; Qin JIA
Chinese Journal of Nursing 2024;59(22):2693-2699
Objective To construct a rehabilitation care platform for spinal cord injury patients,based on patient portrait technology and to validate its application effect.Methods Artificial intelligence technology was used to realize the fusion of data.We constructed a patient portrait rehabilitation nursing system that can provide systematic and personalized information support.By the convenience sampling method,53 perioperative patients with spinal cord injury from July 2023 to December 2023 were selected as the test group to implement the intelligent intervention based on patient portrait technology;53 perioperative patients with spinal cord injury who were hospitalized from January 2023 to June 2023 were selected as the control group to implement the conventional information support intervention.The self-efficacy,self-care ability,and quality of life were compared before the intervention,and 2 weeks,4 weeks,12 weeks after the intervention between the 2 groups.Results 45 cases in the experimental group and 43 cases in the control group reached the endpoint of the study after 12 weeks of intervention.The ANOVA of the 2 groups showed the test group having a greater advantage over the control group,with statistically significant differences in self-efficacy,ability to perform daily living tasks,and quality of life between groups,intergroup effect,and interaction effect(P<0.05).Conclusion The rehabilitation care platform based on patient portraits has a positive effect on improving self-efficacy,self-care ability and quality of life for spinal cord injury patients.

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