ObjectiveTo explore the diagnostic value of resting-state functional magnetic resonance imaging (rs-fMRI) for mild cognitive impairment (MCI) stage of Alzheimer's disease (AD), and to investigate the changes in brain functional connectivity in default mode network (DMN) and medial temporal lobe (MTL) regions. MethodsLiteratures were retrieved from multiple databases including CNKI, PubMed, Medline, and Embase, etc. from January, 2020 to October, 2025, investigating the changes in functional connectivity of DMN and MTL in patients with MCI compared to health control (HC) using rs-fMRI. Two researchers independently screened and extracted the literatures and methodological quality was assessed using QUADAS-2. Review Manager 5.4 was used to perform a meta-analysis of neuroimaging indicators in MCI patients and HC subjects. Stata and SDM were utilized to summarize diagnostic efficacy and brain functional connectivity, calculating the over all sensitivity, specificity and summary receiver operating characteristic-area under the curve (SROC-AUC). Deeks funnel plots were drawn, literature weights were analyzed, and subgroup analyses were conducted. ResultsA total of ten literatures were ultimately included, involving 1 010 patients with MCI and 1 714 HC subjects. MCI patients showed decreased or abnormal blood oxygen level dependence signals in DMN, focusing on bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex. The SROC-AUC was 0.91. In MTL, there was a characteristic decrease of spontaneous neural functional connectivities between the hippocampus and other regions, reflecting the obstruction of information transmission from episodic memory to the central nodes. Abnormal functional connectivity in DMN and MTL resulted in compensatory resting-state functional connectivity enhancement in other subnetworks or local functional connections, such as frontoparietal network and the hippocampal-parietal network. Abnormal activation of mPFC suggested atrophy of the hippocampus or abnormal brain function. The decline in functional connectivity between DMN and MTL indicated impairment of memory and information processing in the early stage. ConclusionThe early functional decoupling between DMN and MTL is a crucial neural mechanism at the MCI stage of AD, providing important neuroimaging evidence for the early diagnosis of AD.

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 investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objective:To investigate the association between prenatal environmental factors and attention defi-cit hyperactivity disorder(ADHD)and its symptom severity in children.Methods:Based on the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)diagnosis criteria,1 156 children with ADHD and 289 normal control children were included in this study.ADHD diagnoses were established using the Clinical Diag-nostic Interview Scale,core symptoms were assessed with the ADHD Rating Scale,and information on prenatal ex-posures were collected via self-developed questionnaires.Results:Maternal stress during pregnancy was associated with increased risk factor of ADHD in children(OR=1.22,P＜0.01).Among children with ADHD,preconception paternal alcohol consumption was positively associated with hyperactivity/impulsivity symptoms(β=0.08,P＜0.05),and maternal smoking during pregnancy was positively associated with total symptoms(β=0.07-0.09,P＜0.05).Conclusion:Maternal stress during pregnancy may increase the risk factor of ADHD in children.Both pre-conception paternal alcohol consumption and maternal smoking during pregnancy may be associated with increased ADHD symptom severity in children.

Objective To present an assessment method based on oscillometric upper-arm cuff pressure wave for realizing home-based detection of arteriosclerosis.Methods An upper-arm cuff pressure wave acquisition device based on an electronic blood pressure monitor was designed to implement data collection for cuff inflation and deflation,as well as the 15 s pressure holding phase.Following preprocessing of the data collected during this holding phase,individual pulse waves were extracted for pulse decomposition analysis(PDA).A novel model that superimposed a logarithmic normal function with two Gaussian functions,and an optimization method that combined template matching and particle swarm optimization were proposed to efficiently and accurately extract PDA features.Gaussian process regression was employed for multifeature fusion analysis,leading to the proposal of a new predictive indicator for arteriosclerosis.Results The mean absolute error of PDA was less than 1.2%,and the average processing time for a single pulse wave was less than 0.2 s.The regression determination coefficient R2 between the obtained indicators and baPWV was 0.8178.Conclusion The analysis on upper-arm cuff pressure wave provides a new reference for non-invasive arteriosclerosis detection,and it can be applied to electronic blood pressure monitors for home-based monitoring,offering significant practical value.

Objective To present an assessment method based on oscillometric upper-arm cuff pressure wave for realizing home-based detection of arteriosclerosis.Methods An upper-arm cuff pressure wave acquisition device based on an electronic blood pressure monitor was designed to implement data collection for cuff inflation and deflation,as well as the 15 s pressure holding phase.Following preprocessing of the data collected during this holding phase,individual pulse waves were extracted for pulse decomposition analysis(PDA).A novel model that superimposed a logarithmic normal function with two Gaussian functions,and an optimization method that combined template matching and particle swarm optimization were proposed to efficiently and accurately extract PDA features.Gaussian process regression was employed for multifeature fusion analysis,leading to the proposal of a new predictive indicator for arteriosclerosis.Results The mean absolute error of PDA was less than 1.2%,and the average processing time for a single pulse wave was less than 0.2 s.The regression determination coefficient R2 between the obtained indicators and baPWV was 0.8178.Conclusion The analysis on upper-arm cuff pressure wave provides a new reference for non-invasive arteriosclerosis detection,and it can be applied to electronic blood pressure monitors for home-based monitoring,offering significant practical value.

Objective To evaluate the clinical efficacy of stellate ganglion block(SGB)combined with intranasal dexmedetomidine for the treatment of insomnia.Methods A total of 64 patients aged 18 to 75 with insom-nia were randomly assigned to either the experimental group(DS group)or the control group(S group).The S group received SGB treatment for 14 consecutive days,whereas the DS group received an additional intranasal dexmedeto-midine spray at a dose of 100 μg,administered 30 minutes before bedtime on days 1 through 6,in conjunction with SGB.We measured and recorded the Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS)scores,and Psychomotor Vigilance Test(PVT)results for both groups at three time points:baseline(T1),the day after treatment(T2),and one month after treatment(T3).Results Intra-group Com-parison:In both the DS and S groups,PSQI scores and dimensionspecific scores at T2 and T3 were significantly lower compared to T1(P<0.05).SAS and SDS scores in both groups showed a significant reduction at T3 compared to T1 and T2(P<0.05),while PVT results exhibited no significant changes(P>0.05).Inter-group Comparison:The PSQI scores and dimensionspecific scores in the DS group at T2(8.44±2.99)and T3(8.22±2.60)were significantly lower than those in the S group at T2(10.88±2.56)and T3(10.88±2.84)(P<0.05).However,no significant differences were observed in SDS and SAS scores between the DS and S groups at T2 and T3(P>0.05).Conclusion Compared to standalone SGB,the combination of SGB with intranasal dexmedetomidine significantly enhances sleep quality in patients with insomnia,while not impacting their levels of anxiety,depression,or alertness.

Gastric ulcer(GU)is one of the common,frequently-occurring and intractable diseases of the digestive system.Spleen-stomach deficiency cold type is the most common and hard-to-cure syndrome pattern of GU,and is both a focus and a challenge in medical research.Therefore,constructing a scientific,reasonable,and clinically practical animal model of GU with spleen-stomach deficiency cold type and formulating objective and effective evaluation criteria are of great significance for in-depth research on the pathogenesis and treatment of GU.In this paper,the methods for constructing GU animal models of spleen-stomach deficiency cold type are comprehensively introduced by systematically reviewing the relevant literature.Firstly,the construction methods of pathological models of GU in Western medicine are introduced,including pyloric ligation method,water immersion-restraint stress method,ethanol-induced method,acetic acid-induced method,etc.This paper expounds the establishment methods for spleen-stomach deficiency cold syndrome type model in traditional Chinese medicine(TCM),including diet disorder method,bitter cold diarrhea method,excessive fatigue method,Qi consumption and Qi impairment method,and overeating sour-flavor method.This paper focuses on the construction methods for disease-syndrome combination GU models of spleen-stomach deficiency cold type,including two-factor modeling method and three-factor modeling method.Meanwhile,the evaluation indices of GU animal models of spleen-stomach deficiency cold type were summarized from various aspects,including animal physical signs(appearance symptoms,animal behavior,and metabolic indices),as well as tissue morphology and molecular biology-related indicators(gastric function,oxidative stress,inflammatory factors,other cytokines,four coagulation parameters,intestinal flora detection),for constructing a comprehensive evaluation system.From the perspective of prescription-based verification,this paper further analyzes the drug composition and pharmacological effects to infer the syndrome type of the treated animal model,so as to verify whether the target animal model is successfully constructed.This review aims to provide a valuable reference for establishing a syndrome-specific GU animal model that closely aligns with clinical reality and embodies the principles of Chinese medicine.This will further advance research on TCM-pattern GU syndromes and deepen the exploration of herbal medicine-based treatments for GU,ultimately promoting the clinical integration and advancement of Chinese medicine in GU therapy.