Alzheimer's disease （AD） is a neurodegenerative disorder characterized by amyloid-β （Aβ） plaque deposition， neurofibrillary tangle （NFT） formation， and chronic neuroinflammation. Its global incidence and mortality continue to rise， yet effective curative therapies remain unavailable. In recent years， dysregulated cholesterol metabolism and immune-inflammatory responses have been increasingly recognized as key drivers of AD pathological progression. Both clinical and experimental studies have shown that patients with AD exhibit disrupted cholesterol homeostasis and aberrant T-cell function， with a significant correlation between these alterations， suggesting that cholesterol metabolic disturbances may participate in and amplify neuroinflammatory responses by modulating T-cell differentiation and activation states. This review systematically delineates the coupling relationship among cholesterol homeostasis imbalance， T-cell abnormalities， AD neuroinflammation， and related pathological injury. Specifically， we summarize the immunometabolic pathological links spanning the peripheral and central compartments， ranging from the effects of peripheral cholesterol metabolic disturbances on T-cell activation， differentiation， and blood-brain barrier permeability to the regulatory role of impaired brain cholesterol homeostasis in infiltrating T-cell inflammatory responses， glial activation， and neural microenvironment remodeling. We further highlight how abnormalities in cholesterol synthesis， transport， efflux， and oxidative product accumulation promote Th17/Treg imbalance， enhanced CD8⁺ T-cell effector activity， increased inflammatory cytokine release， as well as Aβ deposition， blood-brain barrier disruption， glial activation， and neuronal injury. In addition， we review recent progress in natural herbal formulas and bioactive phytochemicals that alleviate T-cell abnormalities and neuroinflammation through restoration of cholesterol homeostasis. Taken together， current evidence suggests that cholesterol homeostasis imbalance is not only a fundamental metabolic abnormality in AD， but may also construct and amplify AD neuroinflammation and related pathological injury by reshaping T-cell immunophenotypes. Therefore， immunometabolic intervention strategies aimed at restoring cholesterol homeostasis may provide a new theoretical basis for mechanistic studies and multi-target prevention and treatment of AD.

ObjectiveTo investigate the effect of schisanlactone E in ameliorating neuroinflammation and synaptic injury in APP/PS1 mice and to elucidate whether its mechanism is related to the regulation of helper T cell 17 （Th17）/regulatory T cell （Treg） immune balance. MethodsAPP/PS1 transgenic mice were assigned into model， low- and high-dose （2 mg·kg^-1·d^-1 and 4 mg·kg^-1·d^-1， respectively） schisanlactone E， and donepezil （1 mg·kg^-1·d^-1） groups. C57BL/6J mice were used as the control group. Each group received the corresponding drug by gavage for 30 days. Learning and memory abilities were assessed by the Morris water maze and novel object recognition tests. The percentages of Th17 and Treg cells in the peripheral blood were analyzed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt （RORγt）， interleukin （IL）-17A， forkhead box protein 3 （FoxP3）， and IL-4 in the hippocampus were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The synaptic ultrastructure in the hippocampus was observed by transmission electron microscopy. The protein levels of synapsin Ⅰ and postsynaptic density protein 95 （PSD95） in the hippocampus were measured by Western blot. Aβ aggregation and microglial activation in the hippocampus were observed by immunofluorescence staining. The mRNA levels of tumor necrosis factor （TNF）-α， IL-6， and IL-1β in the hippocampus were determined by Real-time PCR. ResultsCompared with the control group， the model group showed prolonged escape latency （P<0.05）， decreased time spent in the target quadrant， platform crossings， novel object exploration time， and percentage of novel object contact frequency （P<0.05， P<0.01）， increased Aβ aggregation in the hippocampal tissue （P<0.01）， an increased proportion of Th17 cells （P<0.05）， a decreased proportion of Treg cells （P<0.05）， and an increased Th17/Treg ratio （P<0.01） in the peripheral blood. Furthermore， the hippocampal tissue in the model group exhibited upregulated mRNA levels of RORγt and IL-17A （P<0.05， P<0.01）， downregulated mRNA levels of FoxP3 and IL-4 （P<0.01）， decreased synapses （P<0.05）， decreased PSD density， synaptic interface curvature， and active zone length （P<0.05， P<0.01）， and increased synaptic cleft width （P<0.05）， downregulated protein levels of Synapsin Ⅰ and PSD95 （P<0.01）， increased microglial activation （P<0.01）， and upregulated mRNA levels of TNF-α， IL-6， and IL-1β （P<0.05）. Compared with the model group， the high-dose schisanlactone E group and the donepezil group exhibited shortened escape latency and increased time in the target quadrant and platform crossings （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased novel object exploration time （P<0.05， P<0.01） and percentage of novel object contact frequency （P<0.05， P<0.01）， and reduced hippocampal Aβ aggregation （P<0.05， P<0.01）. The schisanlactone E groups showed a decreased proportion of Th17 cells （P<0.05） and an increased proportion of Treg cells （P<0.05） in the peripheral blood， and all treatment groups showed a decreased Th17/Treg ratio （P<0.05， P<0.01）. The high-dose schisanlactone E group showed a downregulated mRNA level of RORγt in the hippocampal tissue （P<0.05）， and all treatment groups showed a downregulated mRNA level of IL-17A （P<0.05， P<0.01）， and upregulated mRNA levels of FoxP3 and IL-4 （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased synapses， active zone length， synaptic interface curvature， and PSD density， decreased synaptic cleft width （P<0.05， P<0.01）， and upregulated protein levels of synapsin Ⅰ and PSD95 （P<0.05， P<0.01）. The high-dose schisanlactone E group and the donepezil group showed decreased microglial activation in the hippocampus （P<0.01）. The schisanlactone E groups and the donepezil group showed downregulated mRNA levels of TNF-α， IL-6， and IL-1β in the hippocampal tissue （P<0.05， P<0.01）. ConclusionSchisanlactone E significantly improves the cognitive function in APP/PS1 mice by regulating the Th17/Treg immune balance， inhibiting neuroinflammation， and ameliorating synaptic injury.

ObjectiveTo observe the effect of aspirin curcumin ester （CA） on the activation and glucose metabolism reprogramming of the mouse microglia （BV2） model of inflammation induced by high glucose/β-amyloid （Aβ）_1-42， and to explore the potential mechanism of CA in reducing neuroinflammatory response in the brain. MethodsThe BV2 activation model was constructed by high glucose combined with Aβ_1-42 oligomers. BV2 cells were treated with Aβ_1-42 oligomers （10 μmol·L^-1） in a high glucose （50 mmol·L^-1） environment and allocated into normal， high glucose， Aβ， and high glucose + Aβ groups. The cell morphology of each group was observed under a bright field. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to assess the mRNA levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） as well as glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， and pyruvate kinase M2 （PKM2）. To reveal the effects of CA on inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42， this study established the BV2 cell model of inflammatory activation by high glucose and Aβ_1-42 oligomer intervention. The cells were allocated into normal， model （50 mmol·L^-1 glucose + 10 μmol·L^-1 Aβ_1-42）， CA （10 μmol·L^-1）， 2DG （0.2 mmol·L^-1）， and DADA （1 mmol·L^-1） groups. Cell counting kit-8 （CCK-8） was used to detect cell survival rate. The cell morphology of each group was observed under a bright field. The expression of inflammatory factors TNF-α， IL-6， and IL-1β and glycolysis-related key enzymes GLUT1， HK2， PFKFB3， and PKM2 at the mRNA level in each group was measured by real-time PCR. The protein levels of GLUT1， HK2， PFKFB3， and PKM2 were determined by Western blot. The glycolysis rate in each group was measured by seahorse. LC-MS was employed to identify the glucose metabolism intermediates. The morphology of mitochondria in cells was observed by electron microscopy. ResultsConstruction of the BV2 cell model： Compared with the normal group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as those of key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA levels of PKM2 and PFKFB3 （P<0.01）. Effects of CA on the inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42： Compared with the normal group， the model group exhibited amoeboid-shaped cells and cell aggregation， upregulated mRNA levels of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 （P<0.01） and protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， an increased basal glycolysis rate （P<0.01）， a decreased compensatory glycolysis rate （P<0.01）， increased glycolytic intermediates and reduced TCA cycle intermediates. In addition， the mitochondria in the model group exhibited a decreased number （P<0.05）， impaired crista integrity （P<0.01）， an increased proportion of vacuolization （P<0.01）， and abnormal mitochondrial morphology. Compared with those in the model group， the number of amoeboid-shaped BV2 cells reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. All the three treatment groups showed downregulated mRNA levels of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 （P<0.05， P<0.01）， downregulated protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， and slow compensatory glycolysis and basal glycolysis （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to the normal level in all the three treatment groups， with an increase in mitochondrial number （P<0.05）， improved crista integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）. ConclusionAβ_1-42 oligomers can activate BV2 cells and enhance glycolytic activity in the high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the glucose metabolism reprogramming in BV2 cells.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

ObjectiveTo investigate the effect of Danggui Shaoyaosan （DSS） on the morphology and function of mitochondria in rats model of Alzheimer's disease （AD） and its possible mechanism. MethodRats model of AD was established by injection of streptozocin （STZ） into bilateral ventricles of SD rats. The 40 rats were randomly divided into sham group， model group， low， medium and high dosages of Danggui Shaoyaosan （12，24，36 g·kg^-1·d^-1） groups，observed the morphological changes of mitochondria in hippocampus of rats by electron microscopy after 14 days of continuous gavage. In situ end labeling（TUNEL） staining used to detect apoptosis and immunofluorescencereactive used to observe the expression of reactive oxygen species （ROS） and peroxisome proliferators-activated receptor γ coactivator lalpha （PGC-1α），quantitative Real-time polymerase chain reaction（Real-time PCR）detected the mRNA expression of dynamin-related protein 1 （Drp1），mitochondrial fusion protein 2 （MFN2） ，cytochrome C oxidase subunit Ⅳ （COX Ⅳ） and PGC-1α. Western blot detected the protein expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK），phosphorylation（p）-AMPK，recombinant Sirtuin 1 （SIRT1） and PGC-1α. ResultCompared with the sham group，the results of model group showed that the damage of mitochondria in hippocampus was more obvious，accelerated the ROS production and apoptosis rate （P<0.01），decreased the mRNA level of MFN2，COX Ⅳ，PGC-1α，increased the mRNA level of Drp1，and descended the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.05，P<0.01）.Compared with the model group，the medium and high dose of DSS group notably improved the damage of mitochondria，reduced the production of ROS and apoptosis rate （P<0.01），promoted the mRNA expression of MFN2，COX Ⅳ，PGC-1α，inhibited the mRNA expression of Drp1，and up-regulated the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.01）. ResultDSS can significantly ameliorate the mitochondrial homeostasis imbalance in AD rats.

Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.

Objective To evaluate MRI characteristics of solid papillary carcinomas (SPCs) in situ of the breast.Methods A retrospective study included 5 patients with pathologically confirmed SPC in situ was performed.MRI data before operation including conventional MRI,dynamic contrast enhanced MRI (DCE-MRI) and DWI were analyzed.Results All the lesions showed iso/hypointensity on T1 FSPGR sequence,iso/hyperintensity on FSE T2WI sequence and STIR sequence.Mass enhancements were observed for all lesions with oval or irregular shapes on DCE-MRI.The margin of lesions were circumscribed,and internal enhancements were homogeneous or heterogeneous.Time intensity curve appeared a rapid increase in initial contrast phases and platform or outflow types in delayed phases.All the lesions on DWI showed slightly hyperintensity with the ADC value range from 1.34 × 10-3 mm2/s to 1.96)× 10-3 mm2/s.Conclusion MRI manifestations of SPC are characteristics,which may provide valuable information to distinguish SPC in situ from other invasive breast carcinomas.

Objective To investigate the value of kinetic features measured by computer-aided diagnosis (CAD)for breast MRI.Methods One hundred and sixty four lesions diagnosed pathologically by operation or biopsy comprised the analysis set.Automated lesion kinetic information from CADStream programs for breast MRI was identified.Three CAD variables were compared for benign and malignant lesions: initial phase peak enhancement (greatest percentage of signal intensity increase on first contrast enhanced sequence),delayed phase enhancement categorized by a single type of kinetics comprising the largest percentage of enhancement (washout,plateau,or persistent),and delayed phase enhancement categorized by single most suspicious type of kinetics (any washout ＞ any plateau ＞ any persistent).Morphological characteristics of breast lesions were described according to breast imaging and reporting data system (BI-RADS).Initial phase peak enhancement mean values between benign and malignant breast lesions were compared by using Wilcoxon rank-sum test,delayed phase enhancement categorized by a single type of kinetics comprising the largest percentage of enhancement or by single most suspicious type of kinetics between benign and malignant breast lesions were compared by using Chi-square test.Results There were 72 benign and 92 malignant breast lesions.A total of 123 (75.0％) mass lesions were identified,and the other 41 (25.0％) lesions showed no mass.Thirty lesions were BI-RADS-MRI 2,68 lesions were BI-RADS-MRI 3,43 lesions were BI-RADS-MRI 4,23 lesions were BI-RADS-MRI 5.Initial phase peak enhancement mean values of benign and malignant lesions were 237％ (69％ to 629％)and 336％ (86％ to 793％),respectively.There was no significant difference between benign and malignant lesions in initial peak enhancement mean value (Z =-1.626,P =0.104).Delayed phase enhancement categorized by single most suspicious type of kinetics (any washout ＞ any plateau ＞ any persistent) for benign and malignant lesions were 15,10,47 and 2,3,87 respectively.There was a significant difference between benign and malignant lesions (x2 =23.562,P =0.000).Initial peak enhancement value ＜ 100％ or ≥100％ were 5 and 67 for benign lesions,3 and 89 for malignant lesions,respectively.There was no significant difference between benign and malignant lesions at 100％ threshold (x2 =1.181,P =0.277).Delayed phase enhancement categorized by a single type of kinetics comprising the largest percentage of enhancement (washout,plateau,or persistent) for benign and malignant lesions were 48,6,18 and 47,15,30 respectively.There was no significant difference between benign and malignant lesions (x2 =4.496,P =0.106).Conclusions Of CAD kinetics analyzed,only delayed enhancement categorized by most suspicious type is helpful for the differentiation between benign and malignant lesions.However,there is significant overlap between initial peak enhancement at 100％ threshold or delayed kinetics categorized by largest percentage enhancement types of benign and malignant lesions,so lesion morphologic features should be considered.

Objective To evaluate MR diffusion-weighted imaging (DWI)and MR perfusion-weighted imaging(PWI) in differentiating benign from malignant soft tissue tumors by comparing the related parameters. Methods Fifty patients with soft tissue tumors verified by pathology( benign 24, malignant 26) underwent DWI and dynamic contrast-enhanced T2 * -weighted PWI. DWI and PWI data of benign and malignant soft tissue tumors were acquired at the workstation and their difference was analyzed with t-test. The diagnostic accordance rate was verified with x2-test. Subjective overall performance of two techniques were evaluated with receiver operating characteristic (ROC) analysis. Results ADC values of benign and malignant tumors were (2. 03±0. 36) × 10-3 mm2/s, ( 1.52±0. 39) × 10-3 mm2/s,respectively. The signal intensity decrease of them during the first-pass perfusion (SIdecrease ) were ( 13.54 ± 3.37 )%, (47. 57 ± 5. 21 ) % ,respectively. The maximum linearity slope rate of TIC ( SSmax ) of them were ( 5.51 ± 2. 54 ) %, (7.94 ± 3. 33) %, respectively. There were significant differences between benign and malignant tumors of ADC value and SIdecrease ( t = 2. 515,2. 938 ;P < 0. 05 ), while there was no significant difference in SSmax (t = 1. 272,P >0. 05). When the threshold of ADC value was 1. 866 × mm2/s, sensitivity and specificity for determining malignant tumors were 84. 6% (22/26)and 83.3% (20/24). When the threshold of SIdecrease was 40. 33% ,sensitivity and specificity for determining malignant tumors were 88. 5% (23/26)and 75.0% (18/24). In type Ⅰa of TIC,the proportion of benign soft tissue tumor was 3/24 and malignant tumor was 20/26. In type Ⅰb , benign tumor was 14/24 and malignant tumor was 3/26. In type Ⅰc, malignant tumor was 3/26. In type Ⅱ ,benign tumor was 7/24. The diagnostic accordance rate of DWI and PWI were 84. 0% (42/50) and 82. 0% (41/50), respectively. There was no significant difference between them ( x2 = 0. 8, P >0. 05). The accuracies of them were 81.7% , 83. 6% respectively by the area under the ROC curve (AUC). The sensitivity of PWI in diagnosing malignant soft tissue tumors was higher. Conclusions ADC value and SIdecrease are Valllable diagnostic parameters in differentiating benign and malignant soft tissue tumors. The threshold of these parameters for diagnosing malignant soft tissue tumors are 1. 866 × 10-3 mm2/s and 40. 33%, respectively. The type of TIC can help to distinguish malignant tumors from benign tumors, while the SSmax can not. The accuracies of DWI and PWI in the diagnosis of malignant soft tissue tumors are moderate. Compared with DWI, PWI should be selected firstly because of its higher sensitivity in diagnosing malignant tumors.