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.

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.

Objective:To summarize the early clinical outcomes of aortic valve replacement(AVR) using the Perceval sutureless aortic valve.Methods:This retrospective study included 50 patients who underwent AVR with the Perceval sutureless prostheses at Beijing Anzhen Hospital between June 2023 and January 2025. Surgical parameters, early clinical outcomes, valve function, and hemodynamic performance were evaluated to summarize clinical effectiveness.Results:The mean age of patients was(63.5±9.1) years, predominantly female(36/50). Severe aortic stenosis was present in 43 cases(86.0%). A preoperative aortic annulus dimension of 20.0(19.0, 21.0) mm measured in both anteroposterior and transverse diameters. Preoperative peak transvalvular gradient was(92.7±31.0)mmHg(1 mmHg=0.133 kPa), with a mean gradient of (58.0±21.2) mmHg. All procedures were successfully completed using the Perceval sutureless prostheses. Isolated AVR was performed in 20 patients(40.0%), with cardiopulmonary bypass and aortic cross-clamp times of 75.0(50.5, 99.5) min and 50.5(29.5, 71.5) min, respectively. Postoperative transesophageal echocardiography revealed an immediate reduction in the peak transvalvular gradient to 11.0(8.0, 18.0) mmHg, significantly lower compared to preoperative measurements( P<0.001). Two cases of paravalvular leakage and one case requiring permanent pacemaker implantation were reported postoperatively. All patients completed the 3-month follow-up, with one death during the follow-up period; the remaining patients exhibited normal prosthetic valve function without major adverse cardiovascular events. Significant postoperative reductions were observed in left ventricular end-diastolic diameter(45.8 mm vs. 43.2 mm, P=0.003) and left atrial diameter(53.9 mm vs. 44.6 mm, P<0.001) compared with baseline. Conclusion:AVR using the Perceval sutureless prostheses demonstrated safe and effective early clinical outcomes with excellent hemodynamic performance and low incidence of postoperative paravalvular leakage and permanent pacemaker implantation. The sutureless technique represents a viable alternative strategy, particularly advantageous for patients with small aortic annuli or complex surgical conditions, warranting broader clinical adoption.

Objective:To determine the reference interval of IL-10 level in cerebrospinal fluid of adults using multiplex bead-based flow fluorescent immunoassay(MBFFI).Methods:A total of 743 patients without tumor were involved and grouped by diagno-sis.Cerebrospinal fluid and plasma IL-10 were tested by MBFFI.Results:①Cerebrospinal fluid IL-10 levels of the central nervous system infection group were higher than those of other groups.②The cranial venous sinus thrombosis(CVST)group without tumor,in-fection or inflammatory disease were chosen as nearly normal population.As the distribution of cerebrospinal fluid IL-10 levels in these 250 CVST patients were skewed,95％cut-off level was chosen as upper limit and cerebrospinal fluid IL-10<3.50 pg/ml was the refer-ence interval.③No correlation was found between plasma and cerebrospinal fluid IL-10 levels in the CVST group.Conclusion:The medical reference interval of cerebrospinal fluid IL-10 by MBFFI in adults are determined in this study,that is<3.50 pg/ml,to pro-vide clinical reference for practical applications.

The nucleophosmin 1(NPM1)muta-tion is one of the most frequent subtypes in acute myeloid leukemia(AML).Under the conditions of FLT3-internal tandem duplications(FLT3-ITD)and/or DNMT3A co-mutations or adverse cytogenetics,the originally favorable prognosis will deteriorate.In recent years,studies have found that multiple endocrine neoplasia protein(Menin)inhibitors tar-geting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX(homeotic gene)and MEIS1(myeloid ecotropic vi-ral integration site 1)in NPM1-mutated AML,dem-onstrating remarkable anti-leukemia activity.This article aims to review the mechanism and clinical research of Menin inhibitors,novel small molecule targeted drugs in NPM1-mutated AML,as well as the resistance mechanism of Menin inhibitors,hop-ing to provide promising approaches for the subse-quent treatment of NPM1-mutated AML patients.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To explore the lifestyle pattern of the physical examination population and analyze its association with metabolic associated fatty liver disease (MAFLD).Methods:This was a cross-sectional study. Based on the data of 196 515 physical examination individuals from the Health Management Center of the Third Xiangya Hospital of Central South University from January 2016 to December 2020, the subjects were grouped and characterized by principal component analysis and cluster analysis. Among them, 137 277 cases with MAFLD diagnosis information were included in the association analysis between lifestyle pattern and MAFLD. The differences in lifestyle pattern choice among different age, sex, education level, marital status, occupational category and medical insurance type and their differences with the risk of MAFLD were analyzed. The generalized linear mixed model was used to control confounding factors and then association analysis was conducted.Results:There were 6 types of lifestyle patterns in the physical examination population, which were respectively: indulgent type-both physical and mental damage, remedial type-excessive diet, giving type-unique intensity, comfortable type-natural health, heavy smoking type-sedentary injury, heavy drinking type-attempting to make up, accounting for 7.29%, 9.62%, 7.43%, 52.16%, 9.77%, 13.73% in the population. Among them, the male lifestyle pattern was mainly the indulgent type, the remedial type, the heavy smoking type and the heavy drinking type, showing the characteristics of unhealthy lifestyle pattern; Women tended to have healthier lifestyle patterns. After association analysis with MAFLD, it was found that the prevalence of MAFLD was more than 50% in the people who belonged to the indulgent type, remedial type, the heavy smoking type and the heavy drinking type (53.62%, 57.06%, 51.25% and 50.50%, respectively), and the prevalence of MAFLD in the giving type group was 40.17%. The risk of MAFLD in comfortable group was relatively low (28.25%), and the difference in risk of MAFLD among all modes was statistically significant after controlling for confounding factors ( P<0.001). Conclusion:According to cluster mining, there are 6 types of lifestyle patterns in the physical examination population, and the healthier lifestyle pattern has a lower risk of MAFLD.

Objective:To summarize the early clinical outcomes of aortic valve replacement(AVR) using the Perceval sutureless aortic valve.Methods:This retrospective study included 50 patients who underwent AVR with the Perceval sutureless prostheses at Beijing Anzhen Hospital between June 2023 and January 2025. Surgical parameters, early clinical outcomes, valve function, and hemodynamic performance were evaluated to summarize clinical effectiveness.Results:The mean age of patients was(63.5±9.1) years, predominantly female(36/50). Severe aortic stenosis was present in 43 cases(86.0%). A preoperative aortic annulus dimension of 20.0(19.0, 21.0) mm measured in both anteroposterior and transverse diameters. Preoperative peak transvalvular gradient was(92.7±31.0)mmHg(1 mmHg=0.133 kPa), with a mean gradient of (58.0±21.2) mmHg. All procedures were successfully completed using the Perceval sutureless prostheses. Isolated AVR was performed in 20 patients(40.0%), with cardiopulmonary bypass and aortic cross-clamp times of 75.0(50.5, 99.5) min and 50.5(29.5, 71.5) min, respectively. Postoperative transesophageal echocardiography revealed an immediate reduction in the peak transvalvular gradient to 11.0(8.0, 18.0) mmHg, significantly lower compared to preoperative measurements( P<0.001). Two cases of paravalvular leakage and one case requiring permanent pacemaker implantation were reported postoperatively. All patients completed the 3-month follow-up, with one death during the follow-up period; the remaining patients exhibited normal prosthetic valve function without major adverse cardiovascular events. Significant postoperative reductions were observed in left ventricular end-diastolic diameter(45.8 mm vs. 43.2 mm, P=0.003) and left atrial diameter(53.9 mm vs. 44.6 mm, P<0.001) compared with baseline. Conclusion:AVR using the Perceval sutureless prostheses demonstrated safe and effective early clinical outcomes with excellent hemodynamic performance and low incidence of postoperative paravalvular leakage and permanent pacemaker implantation. The sutureless technique represents a viable alternative strategy, particularly advantageous for patients with small aortic annuli or complex surgical conditions, warranting broader clinical adoption.

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.

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.