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 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.

Objective:To investigate the predictive value of quantitative parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in lymph node metastasis of breast cancer.Methods:A retrospective study was conducted on 98 breast cancer patients admitted to our hospital from Jan. 2021 to Dec. 2022. All patients underwent DCE-MRI before surgery and were followed up for 2 years. Finally, 16 cases of lymph node metastasis were confirmed and included in the metastasis group, and the remaining 82 cases without metastasis were included in the non- metastasis group. The clinical data, preoperative routine MRI features and DCE-MRI quantitative parameters of the two groups were analyzed and compared, and the predictive value of DCE-MRI quantitative parameters was analyzed by receiver operating characteristic curve (ROC) .Results:There was no statistically significant difference in age, course of disease and pathological type between the two groups ( t=0.65, 1.43, χ2=1.33, P>0.05) ; The proportion of patients with middle or high pathological grade in metastasis group was higher than that in non-metastasis group ( χ2=11.29, P<0.05). The maximum diameter, shape, internal enhancement pattern and time intensity curve type showed no statistically significant difference ( t=0.54, χ2=3.51, 0.67, 0.42, P>0.05) ; The proportion of patients with blurred edge features in metastasis group was higher than that in the other group ( χ2=4.53, P<0.05). The volume transfer constant (K trans) and reflux rate constant (Kep) in the metastasis group were higher than those in the other group ( t=2.97, 3.22, P<0.05), and extracellular space volume ratio (Ve) showed no statistically significant difference ( t=0.42, P>0.05). Receiver operating characteristic curve (ROC) results showed that the area under the curve (AUC) of K trans, Kep and their combined prediction of breast cancer lymph node metastasis was 0.758, 0.710 and 0.764, respectively, and the sensitivity was 56.25%, 42.75% and 62.50%, respectively. The specificity was 86.59%, 89.02% and 86.59% (all P<0.05) . Conclusions:Quantitative parameters of DCE-MRI can be used to predict lymph node metastasis of breast cancer, among which K trans, Kep and their combination are more effective in diagnosis.

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 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.

Objective:To investigate the predictive value of quantitative parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in lymph node metastasis of breast cancer.Methods:A retrospective study was conducted on 98 breast cancer patients admitted to our hospital from Jan. 2021 to Dec. 2022. All patients underwent DCE-MRI before surgery and were followed up for 2 years. Finally, 16 cases of lymph node metastasis were confirmed and included in the metastasis group, and the remaining 82 cases without metastasis were included in the non- metastasis group. The clinical data, preoperative routine MRI features and DCE-MRI quantitative parameters of the two groups were analyzed and compared, and the predictive value of DCE-MRI quantitative parameters was analyzed by receiver operating characteristic curve (ROC) .Results:There was no statistically significant difference in age, course of disease and pathological type between the two groups ( t=0.65, 1.43, χ2=1.33, P>0.05) ; The proportion of patients with middle or high pathological grade in metastasis group was higher than that in non-metastasis group ( χ2=11.29, P<0.05). The maximum diameter, shape, internal enhancement pattern and time intensity curve type showed no statistically significant difference ( t=0.54, χ2=3.51, 0.67, 0.42, P>0.05) ; The proportion of patients with blurred edge features in metastasis group was higher than that in the other group ( χ2=4.53, P<0.05). The volume transfer constant (K trans) and reflux rate constant (Kep) in the metastasis group were higher than those in the other group ( t=2.97, 3.22, P<0.05), and extracellular space volume ratio (Ve) showed no statistically significant difference ( t=0.42, P>0.05). Receiver operating characteristic curve (ROC) results showed that the area under the curve (AUC) of K trans, Kep and their combined prediction of breast cancer lymph node metastasis was 0.758, 0.710 and 0.764, respectively, and the sensitivity was 56.25%, 42.75% and 62.50%, respectively. The specificity was 86.59%, 89.02% and 86.59% (all P<0.05) . Conclusions:Quantitative parameters of DCE-MRI can be used to predict lymph node metastasis of breast cancer, among which K trans, Kep and their combination are more effective in diagnosis.

OBJECTIVE To analyze the efficacy and safety of luspatercept in the treatment of myelodysplastic syndromes （MDS） anemia， and provide reference for clinical medication. METHODS The literature related to luspatercept for MDS anemia in PubMed， Cochrane Library， Embase and Web of Science were searched by computer， and the search time was from the establishment of the database to January 2024. The quality of literature was evaluated after they were screened according to inclusion and exclusion criteria， the single-group rate meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software， and the subgroup analysis was conducted. RESULTS A total of 756 patients in 9 articles were included in this study. The results of meta-analysis showed that the proportion of MDS patients who reached ≥8 weeks of red blood cell transfusion independence （RBC-TI） was 46% after using luspatercept [95%CI （0.28， 0.64）， P＜0.000 01]. The proportion of MDS patients whose hematological improvement in erythrocyte （HI-E） was 59% [95%CI （0.43， 0.74）， P＜0.000 01]. Among them， 5 articles reported that the proportion of MDS patients with grade 3-4 adverse reactions was 14% [95%CI （0.07， 0.22）， P＝0.000 2]， and the poor general condition， infection， blood and lymphatic system disease were the common adverse reactions. Subgroup analysis showed that the source of heterogeneity was the blood transfusion burden in the proportion of MDS patients with RBC-TI≥8 weeks， and the source of heterogeneity was the 0931-8356251。revised international prognostic scoring system （IPSS-R） risk grade， SF3B1 mutation status and blood transfusion burden in the proportion of MDS patients with HI-E. Sensitivity analysis showed that the results of this study were stable. CONCLUSIONS Luspatercept can significantly improve blood transfusion dependence， reduce blood transfusion burden and promote hematology improvement in MDS patients. But attention should be paid to the occurrence of grade 3-4 adverse events； adverse events such as poor general condition， infection， blood and lymphatic system diseases are more common.

Objective To investigate the impact of nucleophosmin 1-mutated(NPM1m)subtypes,variant allele frequency(VAF)and co-mutations on the survival outcomes of patients with acute myeloid leukemia(AML).Methods Clinical data,mutation status,and outcomes of 86 NPM1m-AML patients admitted in Department of Hematology,First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed.Spearman correlation analysis,Kaplan-Meier curve analysis,Log-rank test,and Cox regression analysis was applied for correlation analysis,survival analysis,and factors affecting survival.Results The overall survival(OS)was significantly shorter in the Rares subtype of NPM1m than the ABD subtype(median OS:164 d vs 416 d,P=0.043).The VAF of NPM1m was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase(LDH)level(P<0.05).OS was reduced when VAF was≥0.37(median OS:164 d vs 730 d,P=0.003).The presence of myelodysplasia-related gene(MR)mutations was associated with a poorer prognosis when compared to the MR wild-type(median OS:45 d vs 395 d,P<0.001).The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)and DNMT3A also indicated a worse prognosis than the non-triple mutation(median OS:173 d vs 483 d,P=0.007).The presence of PTPN11 mutations was associated with improved OS(median OS:395 d vs 240 d,P=0.027),while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients(median OS:662 d vs 189 d)though no statistical significance(P=0.070).Multivariate analysis revealed that LDH(HR=1.002,95%CI:1.000～1.003,P=0.005),NPM1m VAF(HR=2.415,95%CI:1.208～4.829,P=0.013),Rares subtype(HR=3.037,95%CI:1.134～8.136,P=0.027),and MR mutations(HR=5.283,95%CI:1.991～14.017,P<0.001)were independent risk factors associated with OS in the patients.Conclusion Molecular heterogeneity of NPM1m should be taken into account in prognostic stratification of NPM1m-AML.Factors including the Rares subtype,VAF≥0.37,coexistence of FLT3-ITD and DNMT3A mutations,and MR mutations are associated with poor prognosis of NPM1m-AML.The presence of PTPN11 mutations improves the prognosis,while the presence of N/KRAS mutations shows a trend toward better prognosis.LDH,NPM1m VAF,Rares subtype,and MR mutations are independent risk factors affecting OS of patients with NPM1m-AML.

OBJECTIVES: Cardiovascular disease (CVD) poses a major threat to global health. Evaluating atherosclerosis in asymptomatic individuals can help identify those at high risk of CVD. This study aims to establish an individualized nomogram prediction model to estimate the risk of vascular plaque formation in asymptomatic individuals. METHODS: A total of 5 655 participants who underwent CVD screening at the Health Management Center of The Third Xiangya Hospital, Central South University, between January 2022 and June 2024 we retrospectively enrolled. Using simple random sampling, participants were divided into a training set (n=4 524) and a validation set (n=1 131) in an 8꞉2 ratio. Demographic and clinical data were collected and compared between groups. Multivariate logistic regression analysis was used to identify independent factors associated with vascular plaques and to construct a nomogram prediction model. The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). RESULTS: The mean age of participants was 52 years old. There were 3 400 males (60.12%). The overall detection rate of vascular plaque in the screening population was 49.87% (2 820/5 655). No statistically significant differences were observed in clinical indicators between the training and validation sets (all P>0.05). Multivariate Logistic regression analysis identified age, systolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a), male sex, smoking history, hypertension history, and diabetes history as independent risk factors for vascular plaque in asymptomatic individuals (all P<0.05). The area under the curve (AUC) of the nomogram model for predicting vascular plaque risk were 0.778 (95% CI 0.765 to 0.791, P<0.001) in the training set and 0.760 (95% CI 0.732 to 0.787, P<0.001) in the validation set. The Hosmer-Lemeshow goodness-of-fit test indicated good model calibration (training set: P=0.628; validation set: P=0.561). The calibration curve plotted using the Bootstrap method demonstrated good agreement between predicted probabilities and actual probabilities. DCA showed that the nomogram provided a clinical net benefit for predicting vascular plaque risk when the threshold probability ranged from 0.02 to 0.99. CONCLUSIONS The nomogram prediction model for vascular plaque risk, constructed using readily available and cost-effective physical examination indicators, exhibited good predictive performance. This model can assist in the early identification and intervention of asymptomatic individuals at high risk for cardiovascular disease.
Humans ; Male ; Middle Aged ; Female ; Nomograms ; Retrospective Studies ; Risk Factors ; Plaque, Atherosclerotic/diagnosis* ; Aged ; Adult ; Physical Examination ; Logistic Models ; Cardiovascular Diseases/epidemiology* ; ROC Curve