ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

Objective: To observe the distribution characteristics of sex differences in physical growth among children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024, so as to provide clues for improving growth assessment standards and promoting the health of children and adolescents. Methods: Using publicly available height and weight data for children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024 released by the statistics agency of the Taiwan education authorities, sex difference indices were analyzed. Growth curve charts and Pearson correlation were used to analyze the correlation between height/weight and year, as well as trends of change with age and year. These were compared with data from the 8th National Survey on Students Constitution and Health in 2019, covering Han and ethnic minority groups aged 6-15 years in mainland China. Results: The sex difference index for height among children and adolescents in Taiwan, China ranged from -1.20% to 6.67%, showed a trend of decreasing first and then increasing with age. The sex difference index for weight ranged from 3.76% to 19.15%, exhibited an age related trend of a slight initial increase, followed by a decrease, and then an increase. The sex difference indices for height in the 12-15 age groups and for weight in the 15-year-old group were positively correlated with the year ( r =0.74, 0.66, 0.61, 0.92 ; 0.63), while the sex difference indices for weight in the 6-8 age groups were negatively correlated with the year ( r =-0.71, -0.77, -0.53) (all P <0.05). In 2024, the height of children and adolescents in Taiwan, China increased gradually with age, but the growth rate for girls slowed down after age 12. A "two crossover" was observed in height between boys and girls, with boys being taller than girls in the 6-9 age range and after age 12. Weight for both sexes gradually increases with age, but boys have greater weight than girls at all ages. In 2019, the sexual differences in body size among children and adolescents in the Taiwan region, China (the sex difference indices for height:-0.96% to 6.49%；the sex difference indices for weight:4.69%-17.89%) fell within the variation ranges of counterparts in mainland China (the sex difference indices for height:-5.43% to 7.69%；the sex difference indices for weight:-10.12% to 21.56%). Conclusion The sex differences in physical growth among children and adolescents in Taiwan, China are dynamically changing with age and over the long term.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

Objective:To analyze the application value of ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) classification in the differential diagnosis of thyroid nodules and its correlation with patients' midkine, thymidine kinase 1, and thyroid function indicators.Methods:This study was a prospective study. A total of 108 patients with thyroid nodules (120 nodules) who visited Jinan 2 nd People's Hospital from December 2022 to February 2024 were included. Ultrasound examinations were conducted to complete the TI-RADS classification, and serum levels of midkine (MK) and thymidine kinase 1 (TK1), as well as thyroid function indicators, were measured. Based on the patients' pathological results, the consistency between the TI-RADS diagnostic results and the pathological findings was analyzed. The diagnostic efficacy of TI-RADS classification was calculated. The incidence of malignant nodules across various TI-RADS categories was assessed, and the differences in serum levels of MK, TK1, and thyroid function indicators between patients with benign and malignant nodules were compared. Additionally, a correlation analysis was performed to analyze the correlation between the TI-RADS classification of thyroid nodules and the serum levels of MK, TK1, and thyroid function indicators. Results:Pathological examination results revealed 38 malignant nodules and 82 benign nodules. The consistency between ultrasound TI-RADS classification diagnoses and pathological results was good ( Kappa = 0.90, P < 0.001), with diagnostic sensitivity, specificity, and accuracy of 86.84% (33/38), 97.56% (80/82), and 94.17% (113/120), respectively. Among the ultrasound TI-RADS classifications, the malignant rates for category Ⅳb and category Ⅴ thyroid nodules were the highest, at 92.00% (23/25) and 100.00% (10/10), respectively. Serum levels of MK, TK1, and thyroid-stimulating hormone (TSH) were significantly higher in patients with malignant thyroid nodules than in those with benign thyroid nodules (all P < 0.05). Correlation analysis indicated that TI-RADS classification was positively correlated with serum levels of MK, TK1, and TSH ( r = 0.56, 0.60, 0.52, all P < 0.05). Conclusions:Ultrasound TI-RADS classification can be used to differentiate the nature of thyroid nodules, demonstrating high accuracy with low risks of missed or misdiagnoses. It is also closely related to indicators such as MK, TK1, and TSH, providing a basis for the detection of thyroid cancer.

Objective:To analyze the correlation between neutrophil-to-lymphocyte (NLR) and urinary albumin-to-creatinine ratio (UACR) in patients with diabetic nephropathies (DN).Methods:A total of 200 patients with DN admitted to the Endocrinology Department of the Sunshine Xinkang Hospital of Huainan from January 2020 to June 2022 were included, and 167 patients with simple type 2 diabetes mellitus (T2DM) admitted during the same period were randomly included. Clinical baseline data of all patients were collected, and indexes such as NLR and UACR were detected in the two groups. Pearson correlation analysis was used to evaluate the correlation between the above indicators and clinical indicators of diabetic nephropathy, and multi-factor logistic regression analysis was used to evaluate the influencing factors of the occurrence of DN. Receiver operating characteristic (ROC) curve was used to analyze the clinical value of DN recognition.Results:The diabetes course, glycated hemoglobin A 1c (HbA 1c), creatinine (Cr), blood urea nitrogen (BUN), NLR, interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP) and UACR levels in DN group were significantly higher than those in the T2DM group, but the estimated glomerular filtration rate (eGFR) in the DN group was significantly lower than that in the T2DM group (all P<0.05). Pearson correlation analysis showed that UACR was positively correlated with NLR ( r=0.595, P<0.001), HbA 1c ( r=0.642, P<0.01), Cr ( r=0.469, P=0.014) and IL-6 ( r=0.395, P=0.037). It was negatively correlated with eGFR ( r=-0.483, P<0.01). Multivariate logistic regression analysis showed that the duration of diabetes mellitus, HbA 1c, UACR and NLR were independent risk factors for the development of DN in T2DM patients ( OR=2.87, 1.14, 1.44, 2.01, all P<0.05). ROC curve showed that UACR had the highest clinical value in the diagnosis of DN, and its area under the curve (AUC) (95% CI) was 0.90 (0.86-0.94), which was significantly higher than NLR and HbA 1c (all P< 0.05). The value of NLR in the diagnosis of DN was higher than that of HbA 1c, with AUC of 0.83 (0.78-0.88) and 0.76 (0.70-0.82), respectively ( P<0.05). Conclusions:The NLR and UACR in peripheral blood of patients with DN are significantly increased, and these indicators are correlated with renal function in patients with DN, and are potential markers for the diagnosis of DN.

OBJECTIVE To investigate the impact of vesicular stomatitis virus envelope glycopro-tein-G(VSV-G)modification on the mucosal immune efficacy of antigen-loaded engineered exosome vaccines.METHODS In vitro experiments:Dendritic cells(DCs)were divided into three groups:cell-control(treated with culture medium),receptor binding domain(RBD)(transfected with plasmid RBD),and RBD+VSV-G(co-transfected with plasmids RBD and VSV-G).Expression levels of RBD and VSV-G were assessed using Western blotting,flow cytometry,and immunofluorescence.Exosomes were extracted via ultracentrifugation,whose morphology,size distribution,and marker proteins were analyzed using transmission electron microscopy,nanoparticle tracking analysis,and Western blotting that confirmed the expressions of RBD and VSV-G in the exosomes.In vivo experiments:① Female BALB/c mice were divided into the control group Mock exosomes(Mock-Exo)(derived from the supernatant of cell-control),RBD decorated exosomes(RBD-Exo)(derived from the RBD cell supernatant),and RBD and VSV-G decorated exosomes(RBD+VSV-G-Exo)(derived from RBD+VSV-G cell supernatant).Follow-ing intranasal immunization with the respective vaccines,the nasal retention effects were evaluated using in vivo imaging.Flow cytometry was used to assess the ability to recruit immune cells to the nasal tissue.Serum RBD-specific immunoglobulin G(IgG)and mucosal immunoglobulin A(IgA)(bronchoal-veolar lavage fluid/nasal wash)were quantified at 7 and 21 d post-immunization by enzyme-linked immuno-sorbent assay.Body weight changes were monitored and key serum biochemical parameters along with histopathological damage to major organs were analyzed following immunization.② Female BALB/c mice were divided into the Mock-Exo group(intranasally inoculated with Mock-Exo),RBD+VSV-G-Exo group(intranasally inoculated with RBD+VSV-G-Exo),and RBD+VSV-G-Exo(im)group(intramus-cularly injected with RBD+VSV-G-Exo).RESULTS In vitro experiments:RBD and VSV-G were successfully expressed in cells,with positive rates of RBD+and VSV-G+cells at 64.4%and 31.2%,respectively.The extracted exosomes exhibited regular morphology and qualified purity,with a particle size of approximately 138 nm and successfully loaded RBD and VSV-G proteins.In vivo experiments:Compared to Mock-Exo and RBD-Exo,RBD+VSV-G-Exo prolonged nasal retention time to 96 h and markedly increased the numbers of CD49B+natural killer cells,CD11c+dendritic cells,and F4/80+macrophages in nasal tissues.RBD+VSV-G-Exo induced robust RBD-specific immune responses,with serum IgG titers,BALF IgA titers,and nasal wash IgA titers reaching 1∶5 215,1∶2 560,1∶1 114,respec-tively.In contrast,no RBD-specific IgA antibody titers were detected in the BALF and nasal wash of mice treated with RBD+VSV-G-Exo(im).Mice showed stable body weight gain during 30 d post-immu-nization.Major serum biochemical indices were within normal reference ranges,and no obvious patho-logical changes were observed in major organs or olfactory bulbs 7 d after immunization.CONCLU-SION VSV-G modification extends the retention time of engineered exosome vaccines in nasal tissues,enhance their ability to recruit immune cells,and induce a high-level antigen-specific respiratory mucosal immune response.

Objective:To identify the incidence and prevalence of inflammatory bowel disease (IBD) in the northern Chinese population of Jinan, Shangdong Province, along with its temporal trends from 2005 to 2022.Methods:By utilizing the data from the Jinan basic medical insurance system, a population-based IBD cohort was constructed. This facilitated the computation of both the incidence and prevalence rates of IBD, alongside their temporal trends throughout the 2005 to 2022 timeframe. The 95% confidence intervals were estimated using poisson regression.Results:The overall incidence rate of IBD showed a yearly increasing trend, with age-standardized incidence rates rising from 0.03/100 000 in 2005 to 5.39/100 000 in 2022. The age-standardized incidence rate of ulcerative colitis (UC) increased from 0.03/100 000 in 2005 to 4.97/100 000 in 2022. The age-standardized incidence rate of Crohn's disease (CD) rose from 0.05/100 000 in 2011 to 0.44/100 000 in 2022. The crude prevalence of IBD increased from 0.60/100 000 in 2005 to 32.39/100 000 in 2022. Specifically, the crude prevalence of UC increased from 0.60/100 000 in 2005 to 31.44/100 000 in 2022, while the crude prevalence of CD increased from 0.05/100 000 in 2011 to 1.19/100 000 in 2022.Conclusions:Analysis of recent medical insurance data reveals a continuous uptrend in both the incidence and prevalence of IBD in Jinan, a northern city in China. This underscores the urgent need for enhanced medical resources and healthcare guaruntee to ensure the well-being of individuals afflicted with IBD.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.