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.

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.

AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)recep-tor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthe-sia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was ter-minated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anes-thesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tis-sues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloid β-protein(Aβ),and p-tau were detected by Western blot.RE-SULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points dur-ing anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+in-creased.The protein levels of GluN1 subunit,Aβ and p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves and δ waves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβ and p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLU-SION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power of δ EEG waves,but has no significant effect on recovery time.Me-mantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA recep-tors,Aβ and p-tau,and attenuating neuroinflammation.

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 analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)recep-tor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthe-sia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was ter-minated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anes-thesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tis-sues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloid β-protein(Aβ),and p-tau were detected by Western blot.RE-SULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points dur-ing anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+in-creased.The protein levels of GluN1 subunit,Aβ and p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves and δ waves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβ and p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLU-SION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power of δ EEG waves,but has no significant effect on recovery time.Me-mantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA recep-tors,Aβ and p-tau,and attenuating neuroinflammation.

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 analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

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.