OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Objective:To examine the interaction between gender and the visceral adiposity index (VAI) in relation to the risk of type 2 diabetes mellitus (T2DM).Methods:This retrospective cohort study utilized data from the public Dryad database derived from the NAGALA (NAFLD in the Gifu Area, Longitudinal Analysis) project (1994-2016). Participants were stratified into quartiles based on VAI levels. A multivariate Cox proportional hazards regression model was employed to evaluate whether VAI independently predicts T2DM risk. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were constructed for each VAI quartile. Subgroup analyses were conducted to examine associations across age and body mass index categories. Both multiplicative and additive interaction effects between gender and VAI were assessed. Additionally, gender-specific Cox models were fitted to further explore these associations.Results:A total of 15 453 participants [8 419 males and 7 034 females; mean age, (43.7±8.9) years] were included, with a median follow-up duration of 5.39 years. During follow-up, 373 participants (2.4%) developed T2DM. After adjustment for potential confounders, higher VAI levels were independently associated with increased T2DM risk ( HR=1.16; 95% CI 1.11-1.21), consistent with the results across VAI quartiles. Kaplan-Meier analysis revealed a significant trend of increasing T2DM incidence across VAI quartiles ( P<0.001). The area under the ROC curve for VAI in predicting T2DM at 3, 5, and 10 years was 0.755, 0.735, and 0.696, respectively. Sensitivity analyses showed that elevated VAI was associated with increased T2DM risk across all age and body mass index subgroups (all P<0.05). Regarding interaction analysis, the HR (95% CI) for the multiplicative interaction between VAI and gender was 1.22 (1.19-1.26). The relative excess risk of interaction was -1.08 (95% CI -2.96 to -0.06), the attributable proportion of interaction was -0.54 (95% CI -1.35 to -0.01), and the synergy index was 0.48 (95% CI 0.26-0.91), indicating a negative additive interaction. Using low-VAI women as the reference group, the risk of T2DM in high-VAI women was higher ( HR=2.53, 95% CI 1.59-4.02) compared to high-VAI men ( HR=2.01, 95% CI 1.49-2.72). In gender-specific analyses, increasing VAI remained significantly associated with elevated T2DM risk after adjustment in both females ( HR=1.43, 95% CI 1.21-1.68) and males ( HR=1.16; 95% CI 1.11-1.22), with consistent findings across VAI quartiles. Conclusions:VAI and gender demonstrated multiplicative and additive interaction in relation to T2DM risk. The association between increasing VAI and T2DM risk was more pronounced in women than in men.

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.

Objective:To observe the effects of adipose-derived stem cells(ADSC)combined with acellular scaffold(AS)on the ultrastructure of dorsal root ganglion and the protein and mRNA expression levels of ciliary neurotrophic factor(CNTF),Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phosphorylated STAT3(p-STAT3)in the rats with sciatic nerve injury(SNI),and to clarify the protective effect of ADSC combined with AS on dorsal root ganglion in the SNI rats and its possible mechanism.Methods:The rat ADSCs were isolated and cultured and their multidirectional differentiation potential was detected.The AS of rats was prepared,and ADSCs were injected into the AS to construct tissue-engineered nerve.A total of 36 rats were randomly divided into control group,model group,AS group,and ADSC+AS group.The rats in control group were routinely fed,and the rats in other groups were used to establish the SNI models by resecting 10 mm of right sciatic nerve.The rats in model group received no further treatment,while the rats in AS group and ADSC+AS group were bridged with AS and the constructed tissue-engineered nerve at the two ends of the injured nerve,respectively.At 6 weeks after surgery,transmission electron microscope was used to observe the ultrastructure of dorsal root ganglion of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of CNTF,p-JAK2,and p-STAT3 in dorsal root ganglion of the rats;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of CNTF,JAK2,and STAT3 in dorsal root ganglion of the rats in various groups.Results:After 7 d of primary ADSC culture,a large number of large and long spindle-shaped cells were observed under the inverted microscope,arranged in clusters or whirlpools;red lipid droplets were observed with oil red O staining under microscope,and calcified nodules were observed with Alizarin red staining under microscope,indicating that the isolated and cultured cells had multidirectional differentiation ability.Compared with normal nerve tissue,the level of DNA in AS of rats was significantly decreased(P<0.05).Compared with control group,the nuclear membrane of dorsal root ganglion cells in model group was uneven and serrated,the number of organelles in the cytoplasm was decreased,mitochondria were swollen with broken or missing cristae and unclear structure;the CNTF protein and mRNA expression levels were significantly decreased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly increased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly increased(P<0.01).Compared with model group,the serrated change of nuclear membrane of the dorsal root ganglion cells in AS group was significantly alleviated,the number of organelles in the cytoplasm was increased,and mitochondrial swelling was reduced;in ADSC+AS group,the nuclear membrane of dorsal root ganglion cells tended to be intact,the number of organelles was increased,and mitochondrial swelling and vacuolization were significantly reduced;the CNTF protein and mRNA expression levels in the dorsal root ganglion in AS group and ADSC+AS group were significantly increased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Compared with AS group,the CNTF protein and mRNA expression levels in ADSC+AS group were significantly increased(P<0.05 or P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Conclusion:The application of ADSC combined with AS can improve the ultrastructure of dorsal root ganglion in the SNI rats,and the mechanism may be related to the increased CNTF expression and decreased activation of the JAK2/STAT3 signaling pathway in the dorsal root ganglion by ADSC combined with AS application.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia(VaD)model rats.METHODS VaD rat model was established by bilateral common carotid artery ligation.The experimental animals were randomly divided into sham operation group(SHAM),model group(MOD),Yifei xuanfei jiangzhuo formula low-dose group(YFXF-L),Yifei xuanfei jiangzhuo formula high-dose group(YFXF-H),and Donepezil hydrochloride group(positive control),with 9 animals in each group.After 30 days of intervention,the spatial learning memory ability was assessed by Morris water maze experiment;HE staining was used to observe histopathological changes in CA1 area of hippocampus;ELISA was used to detect the levels of serum inflammatory factors[interleukin-1β(IL-1β)and IL-4];Western blot was used to detect the expressions of heat shock protein 90(HSP90)/mixed lineage kinase domain-like protein(MLKL)/dynamin-related protein 1(Drp1)pathway-related proteins,mitochondrial fusion proteins(MFN1,MFN2),and adenosine triphosphate synthase 5A(ATP5A)in hippocampal tissues.The immunohistochemistry was used to detect the level of phosphorylated MLKL(p-MLKL);real-time fluorescence quantitative PCR was adopted to detect mRNA expressions of HSP90,MFN1,MFN2 and ATP5A.RESULTS Compared with SHAM group,the escape latency of rats in the MOD group was significantly prolonged,the number of crossing the platform was significantly reduced,and the hippocampal tissues showed typical neuronal damage characteristics,the positive expression level of p-MLKL and the serum level of IL-1β significantly increased,while the serum level of IL-4 significantly decreased,the protein and mRNA expression of HSP90,as well as the protein expressions of p-MLKL/MLKL and p-Drp1(Ser616)/Drp1 were all significantly increased in hippocampal tissue,the protein and mRNA expressions of MFN1,MFN2 and ATP5A,and protein expression of p-Drp1(Ser637)/Drp1 were all significantly decreased(P＜0.05).After the intervention of Yifei xuanfei jiangzhuo formula,above indicators in each treatment group were all significantly reversed(P＜0.05).CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway,inhibiting mitochondrial fission,thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.