BACKGROUND:The clearance pathway of metabolic waste in the brain is crucial for maintaining neural homeostasis.The accumulation of metabolic waste disrupts this equilibrium,representing a common pathological feature of many central nervous system diseases.In recent years,research focusing on the glymphatic system has emerged as a hotspot in the nervous system field.OBJECTIVE:To construct a knowledge map of glymphatic system research,visually analyze the current state of research,main hotspots,and future development trends within this area.METHODS:Utilizing CiteSpace,VOSviewer,and the Bibliometrix package in the R language environment,this study conducted an in-depth visual analysis of glymphatic system-related literature from the Web of Science Core Collection database,spanning from January 2012 to March 2024.This analysis included authors,institutions,countries,journals,keywords,and co-citation frequencies.RESULTS AND CONCLUSION:A total of 687 related articles were included in this study.The number of publications in this field increased year by year,showing an explosive growth trend in the past three years.The countries,institutions,and authors with the largest number of publications in this research field were the United States,University of Rochester,and Professor Maiken Nedergaard.The journal with the highest number of publications was JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM.The high-frequent and high-central keywords mainly focused on the mechanism such as cerebrospinal fluid hydrodynamics,neurological diseases such as Alzheimer's disease,and imaging techniques such as diffusion tensor imaging.The literature with the highest co-citation frequency was a classic review of the glymphatic system.The above results show that the research of glymphatic system is an emerging and active field,which has attracted wide attention at home and abroad and gradually expand from theoretical research to clinical practice.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective To investigate the prevalence of metabolic syndrome(MS)and its influencing factors among adult residents in Zhifu district of Yantai city,and to provide data support and scientific basis for relevant departments to formulate policies and measures.Methods A total of 2412 residents in Zhifu district were selected by multi-stage stratified sampling method,and their basic information,personal health status,height,weight,blood pressure,fasting blood glucose,blood lipids and other indicators were collected by questionnaire survey,physical measurement and laboratory examination.The screening of MS was based on the diagnostic criteria of MS recommended by Chinese Diabetes Society(CDS).Results Among the adult residents in Zhifu district,the number of MS patients was 522,with a crude prevalence rate of 21.6%.The prevalence of MS in men was 26.9%higher than that in women(16.9%)(χ2=35.939,P<0.001).With the increase of age,the prevalence rate of MS showed an overall upward trend(linear trend test χ2=150.557,P<0.001).With the increase of education level,the prevalence rate of MS showed an overall downward trend(linear trend test χ2=81.670,P<0.001).The results of multivariate logistic regression analysis further showed that male and age increase were high risk factors for MS;higher education level,unmarried,engaged in static occupation,and increased activity were protective factors for MS.Conclusion The prevalence rate of MS in adult residents in Zhifu district of Yantai is basically equal to the national average level,suggesting that the government and health service institutions at all levels should take health exercise,smoking cessation and alcohol restriction as the entry point for health education and early diagnosis and treatment;meanwhile,targeted interventions should be carried out according to different characteristics of the population.

Objective To provide a scientific basis for cancer prevention and control in Zhifu district and Yantai city by comprehensively describing and analyzing the epidemiological characteristics and disease burden of malignant tumors in Zhifu district,and reduce the disease burden.Methods The data of cancer incidence and mortality collected by the Center for Disease Control and Prevention in Zhifu district from 2010 to 2020 were used to evaluate the incidence and mortality of cancer.The excel template and DismodII software released by WHO were used to calculate the disease burden indexes such as disability-adjusted life year(DALY),years of life lost(YLL),and DALY rate,and the Joinpoint regression model was used to analyze the trend of disease burden,and annual percent change and average annual percent change were calculated.Results The total DALY of malignant tumors in Zhifu district from 2010 to 2020 was 166192.75 person-years,with a DALY rate of 199.02‰.The disease burden of malignant tumors mainly came from YLL,accounting for 74.70%of DALY.Conclusion Zhifu malignant tumor disease burden is on the rise,the relevant departments still need to improve the registration of malignant tumors,improve the knowledge of the population through the way of public welfare propaganda,increase the screening of common malignant tumors,promote the progress of early diagnosis and treatment of cancer,reduce the disease burden brought by early death.To improve the tertiary prevention of malignant tumors.

It is proposed that the brain Xuanfu and the glymphatic system(GS)have commonality in physiological structure and similarity in functions such as transporting brain substances,transmitting brain information and clearing metabolites.It is believed that GS may be the substantial manifestation of the brain Xuanfu,and GS dysfunction is the key pathological link of depression.Xuanfu stagnation and Shenji dysfunction are the core pathogenesis of depression.Taking"Brain Xuanfu-GS"as the starting point,the patho-logical mechanism of depression is deeply explored,providing a theoretical basis for the clinical diagnosis and treatment of depression in traditional Chinese medicine.

Background and purpose:Immune checkpoint blockade(ICB)has become a promising strategy for treating cervical cancer(CC),but terminal T cell depletion still limits the therapeutic efficacy of ICB.The deletion of sorting nexin-9(SNX9)can inhibit thymocyte selection-associated high mobility group box protein(TOX),alleviate T cell exhaustion,and provide new ideas for preventing T cell exhaustion and enhancing the efficacy of cancer immunotherapy.Therefore,this study aimed to explore the immune escape mechanism mediated by the depletion of CD8+T cells induced by the SNX9/TOX signaling pathway in the CC microenvironment.Methods:Fifty-four peripheral blood samples were collected,including 18 from CC patients,18 from patients with high-grade squamous intraepithelial lesions(HSIL)and 18 from subjects with normal cervix.In addition,the study collected 153 pairs of CC and adjacent tissues from patients who received operation in our hospital for the first time.Clinicopathological features,tumor stages,follow-up records and other relevant clinicopathological data of CC patients were obtained from hospital records.The research was approved by the ethics committee of Changsha Fourth Hospital(approval number:20220206).A total of 24 mice were randomly assigned to the following four groups:immunoglobulin G(IgG)group,Anti-SNX9 group,Anti-programmed death-1(PD-1)group and Anti-SNX9+Anti-PD-1 group,with 6 mice in each group.Each group received intraperitoneal injection of blocking antibody and isotype control treatment respectively.ELISpot was used to detect the ability of CD8+T cells to secrete tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).The expressions of TOX and SNX9 in cervical cancer tissues were detected by western blot and immunohistochemistry.Results:The expressions of SNX9 and TOX mRNA in peripheral blood mononuclear cell(PBMC)of CC patients were higher compared with HSIL and normal controls(P＜0.05).The positive cell level of SNX9 and TOX immunohistochemical score were higher in CC tissue than in adjacent tissues(t=18.63,21.10,P＜0.001).The high expression of SNX9 in CC was related to low differentiation/undifferentiation,tumor size,parauterine infiltration,vaginal infiltration,late FIGO stage and pelvic lymph node metastasis(P＜0.05).Compared with the low expression group of SNX9,the overall survival time of CC patients in the high expression group of SNX9 was shorter(P＜0.05).The percentage of CD8+SNX9+T cells was significantly higher in CC patients than in normal controls and HSIL patients(P＜0.05).The ability of CD8+SNX9+T cells to secrete cytokines(TNF-α and IFN-γ)was significantly lower compared with CD8+SNX9-T cells(P＜0.05).Compared with the Anti-SNX9 group,the growth and proliferation of cervical tumor,the expression of SNX9 and TOX protein in tumor tissue in the Anti-SNX9+Anti-PD-1 group further decreased(P＜0.05),and the level of infiltrating CD8+T lymphocytes in tumor tissue and the ability of CD8+T lymphocytes to secrete functional factors TNF-α and IFN-γ further increased(P＜0.05).Conclusion:SNX9/TOX signaling pathway exhibits enhanced activity in patients with cervical cancer and mouse models,and is related to immunosuppression.Targeting SNX9/TOX signaling pathway may be a potential therapeutic strategy for CC.

Objective To compare blood flow velocity measurements obtained using two different color Doppler imaging(CDI)devices with linear probes of varying frequencies.Methods CDI measurements were performed in 99 eyes of 50 participants from Shenyang Aier Excellent Eye Hospital using two different CDI devices,Apogee Type3500 and Esaote MyLab 7 eHD.These measurements included peak systolic velocity(PSV),end-diastolic velocity(EDV),and resistance index(RI)of the ophthalmic artery(OA),central retinal artery(CRA),and short posterior ciliary arteries(SPCA).The differences in measurements between the two devices were analyzed using a paired t-test.The level of agreement between the two CDI devices was calculated using the Bland-Altman method,and the concordance correlation co-efficient(CCC)was calculated.Results There was a statistically significant difference between the two CDI devices in the PSV,EDV of the OA,CRA,and SPCA,and RI of the CRA and SPCA.The PSV and EDV of each vessel were higher in Apogee than in Esaote,and the RI of the CRA and SPCA were lower for Apogee than for Esaote(P＜0.05).The CCC demonstrated poor overall concordance ranging from 0.136 to 0.517.Conclusion The consistency of most measurements obtained from both devices is poor.CDI inter-device reproducibility is unreliable,even when the measurements are conducted consecutively by a single experienced ultrasonographer.

Objective To investigate the prevalence of metabolic syndrome(MS)and its influencing factors among adult residents in Zhifu district of Yantai city,and to provide data support and scientific basis for relevant departments to formulate policies and measures.Methods A total of 2412 residents in Zhifu district were selected by multi-stage stratified sampling method,and their basic information,personal health status,height,weight,blood pressure,fasting blood glucose,blood lipids and other indicators were collected by questionnaire survey,physical measurement and laboratory examination.The screening of MS was based on the diagnostic criteria of MS recommended by Chinese Diabetes Society(CDS).Results Among the adult residents in Zhifu district,the number of MS patients was 522,with a crude prevalence rate of 21.6%.The prevalence of MS in men was 26.9%higher than that in women(16.9%)(χ2=35.939,P<0.001).With the increase of age,the prevalence rate of MS showed an overall upward trend(linear trend test χ2=150.557,P<0.001).With the increase of education level,the prevalence rate of MS showed an overall downward trend(linear trend test χ2=81.670,P<0.001).The results of multivariate logistic regression analysis further showed that male and age increase were high risk factors for MS;higher education level,unmarried,engaged in static occupation,and increased activity were protective factors for MS.Conclusion The prevalence rate of MS in adult residents in Zhifu district of Yantai is basically equal to the national average level,suggesting that the government and health service institutions at all levels should take health exercise,smoking cessation and alcohol restriction as the entry point for health education and early diagnosis and treatment;meanwhile,targeted interventions should be carried out according to different characteristics of the population.

Objective To provide a scientific basis for cancer prevention and control in Zhifu district and Yantai city by comprehensively describing and analyzing the epidemiological characteristics and disease burden of malignant tumors in Zhifu district,and reduce the disease burden.Methods The data of cancer incidence and mortality collected by the Center for Disease Control and Prevention in Zhifu district from 2010 to 2020 were used to evaluate the incidence and mortality of cancer.The excel template and DismodII software released by WHO were used to calculate the disease burden indexes such as disability-adjusted life year(DALY),years of life lost(YLL),and DALY rate,and the Joinpoint regression model was used to analyze the trend of disease burden,and annual percent change and average annual percent change were calculated.Results The total DALY of malignant tumors in Zhifu district from 2010 to 2020 was 166192.75 person-years,with a DALY rate of 199.02‰.The disease burden of malignant tumors mainly came from YLL,accounting for 74.70%of DALY.Conclusion Zhifu malignant tumor disease burden is on the rise,the relevant departments still need to improve the registration of malignant tumors,improve the knowledge of the population through the way of public welfare propaganda,increase the screening of common malignant tumors,promote the progress of early diagnosis and treatment of cancer,reduce the disease burden brought by early death.To improve the tertiary prevention of malignant tumors.

It is proposed that the brain Xuanfu and the glymphatic system(GS)have commonality in physiological structure and similarity in functions such as transporting brain substances,transmitting brain information and clearing metabolites.It is believed that GS may be the substantial manifestation of the brain Xuanfu,and GS dysfunction is the key pathological link of depression.Xuanfu stagnation and Shenji dysfunction are the core pathogenesis of depression.Taking"Brain Xuanfu-GS"as the starting point,the patho-logical mechanism of depression is deeply explored,providing a theoretical basis for the clinical diagnosis and treatment of depression in traditional Chinese medicine.