Objective To investigate the neuroprotective effect of soluble epoxide hydrolase (sEH) inhibitor 12-(3-adamantan-l-yl-ureido) dodecanoic acid (AUDA) on focal cerebral ischemia/reperfusion in rats and its mechanisms.Methods Sixty male Sprague-Dawley rats were randomly divided into sham operation and saline control groups,as well as low-dose (0.157 ml/kg),medium-dose (0.235 ml/kg) and high-dose (0.314 ml/kg) AUDA groups (n =12 in each group).Four rats in each group were selected for infarct volume,cell apoptosis and p-Akt immunohistochemistry detection.A model of middle cerebral artery ischemia/ reperfusion was induced by the suture method.The corresponding dose AUDA or equal volume of saline was injected intraperitoneally before reperfusion in each AUDA group and the saline control group.Neurological deficit scores were performed at 24 h of reperfusion.2,3,5 triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume.TdT-mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic cells of brain tissue in the periinfarction area.Immunohistochemical method was used to detect p-Akt expression of brain tissue in the peri-infarction area.Results TTC staining showed no infarction was observed in the sham operation group.The infarction volumes in the saline control group as well as the low-dose,medlum-dose and high-dose AUDA groups were 254.146 ± 25.481,212.679 ± 7.514,150.188 ± 33.997,and 99.563 ± 3.415 mm3,respectively.There were significant differences (F =39.637,P =0.000).The each dose AUDA group was significant less than the control group (all P=0.000).The medium-dose AUDA group was significantly less than the low-dose AUDA group (P=0.002),and the high-dose AUDA group was also significantly less than the low-dose AUDA group (P =0.000) and medium-dose AUDA group (P =0.006).TUNEL staining showed that a small number of apoptotic cells (6.400 ± 1.477/high-power field) were observed in the sham operation group.The numbers of apoptotic cells in the saline control group as well as in the low-dose,medium-dose and high-dose AUDA groups were 57.550 ± 13.067,47.030 ± 8.423,34.530 ± 4.393 and 26.400 ± 2.683/high power field,respectively.Each dose AUDA group was significantly less than the saline control group (all P ＜0.01).The medium-dose and high-dose AUDA groups were significantly less than the low-dose AUDA group (P ＜ 0.01),and the high-dose AUDA group was also significantly less than the medium-dose AUDA group (P ＜0.01).Immunohistochemistry showed that only a few p-Akt-positive cells (3.325 ± 1.438/high power field) were observed in the sham operation group.The numbers of p-Akt-positive cells in the saline control group as well as the low-dose,medium-dose and high-dose AUDA groups were 9.450 ±2.531,16.400 ± 3.865,22.875 ± 7.974,and 29.300 ± 3.203/high-power field,respectively.Each dose AUDA group was significantly more than the saline control group (all P ＜0.01).The medium-dose and high-dose AUDA groups were significantly more than the low-dose AUDA group (all P ＜0.01).The high-dose AUDA group was also significantly more than the medium-dose AUDA group (P ＜ 0.01).Conclusions The inhibition of sEH may decrease neuronal apoptosis and reduce infarct volume in the peri-infarction area by upregulating the PI3K/Akt pathway.It has a neuroprotective effect for focal cerebral ischemia/reperfusion in rats.

Objective To investigate the association of multi-modality neuroimaging features and cognitive function in mild cognitive impairment (MCI) and Alzheimer's disease (AD).Methods Nine individuals with amnestic MCI (aMCI), fifteen patients with mild probable AD, and eleven age-controlled cognitively normal controls (NC) were recruited.All participants were administered with mini-mental status examination (MMSE) and Cognitive assessment screening instrument (CASI) to assess general cognitive function.Optimized voxel-based morphometry ( VBM ) was used for the analysis with 3-D high resolution anatomical images.Values of fractional anisotropy (FA) and mean apparent diffusivity coefficient (ADC) were measured from different brain regions on diffusion-tensor images ( DTI) .The relationship between structural atrophy and DTI-based measurements in the selected brain regions was examined.Results The scores of MMSE and CASI were correlated with the volumetric changes in such areas as temporal, frontal and parietal lobes, and cingulate gyrus and hippocampal gyrus (P <0.001).The scores of MMSE and CASI were positively correlated with FA values, and negatively with ADC values in the white-matter-affected regions including temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus (P < 0.05).Conclusions Cognitive decline was associated with atrophy and white matter microstructural alterations in temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus in MCI and AD. Multi-modality imaging technique may be important in elucidating the brain mechanism of cognitive impairment.

Objective To evaluate the microstructural integrity of white matter (WM) in mild cognitive impairment ( MCI ) and Alzheimer disease (AD) using DTI technique, and to explore the relationship between WM abnormalities and cognitive dysfunction. Methods Nine cases of amnestic MCI, 15 cases of mild probable AD and 11 cases of normal controls (NC) with normal-appearing WM (NAWM) were studied using 3. 0 T MR system. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in different WM areas. One-way analysis of variance was used to test the difference among the three groups for DTI indices. Spearman Correlation analysis was applied to reveal the correlation between the DTI indices and the MMSE and CASI scores. Results The FA value in parietal, centrum semiovale, posterior cingulate gyrus, parahippocampus, temporal and frontal WM in MCI was 0. 31 ± 0.03,0. 39 ± 0. 03,0. 62 ± 0. 05,0. 59 ± 0. 05,0. 47 ± 0. 08,0. 32 ± 0. 04, respectely, and MD value was ( 899 ± 30 ) × 10-6,(782±53) × 10-6, (732±45) × 10-6, (806±38) × 10-6, (772 ± 55) × 10-6, (792 ± 35) × 10-6 mm2/s. The FA value of these regions in AD was 0. 28 ± 0. 04, 0. 37 ± 0. 03,0. 55 ± 0. 06,0. 52 ± 0.05,0.40±0. 05,0. 27 ± 0. 04,and MD value was (912±37) × 10-6,(800 ± 67) × 10-6, (762 ± 46) × 10-6, (874±57)×10-6,(822±55)×10-6, (822±39)×10-6 mm2/s. The FA value in NC was 0.36±0.03,0.43±0.05,0.64±0.05, 0.60±0.05, 0.52±0.05,0.33±0.03, and MD value was (866±37)×10-6,(754±54)×10-6,(718±32)×10-6,(810±39)×10-6,(755±48) × 10-6, (785±23)×10-6 mm2/s. Compared with NC, the FA value in parietal WM was significantly decreased in MCI(P<0. 01 ), The significantly reduced FA values in parietal, centrum semiovale, posterior cingulate gyrus, parahippocampus, temporal and frontal WM , as well as significantly elevated MD values were found in AD(P <0. 05). There was significant correlation between these DTI indices and MMSE and CASI scores (P<0.05). Conclusions MR DTI can detect WM abnormalities in AD and MCI. The parietal WM abnormalities and the disconnection of WM circuitry may play an important role in the development of dementia.

Objective:To study the effects of Astragalus Root Injection(a traditional Chinese herb medicine) on oxaliplatin-induced apoptosis of hippocampal neurons. Motheds: The primary culture of hippocampus neurons from SD rats (aged within 24h) were treated with different concentrations of oxaliplatin( L-OHP) (0, 3, 5 and 10 ?g/mL) and Astragalus Root Injection (0.05, 0.2 and 0.5 g/mL). The apoptosis of the neurons and the nerve growth factor(NGF)level were analyzed. Results: Astragalus Root Injection dose-dependently decreased neuronal cell apoptosis induced by oxaliplatin (P

Objectives To evaluate the role of PCSK9 (proprotein convertase subtilisin kexin type 9) on the lipid accumulation and kidney injury of C57BL/6 mice. Methods The 24 h urine of 12 weeks old wide type C57BL/6 mice and PCSK9 knockout (KO) mice were collected through a metabolic cage, followed by perfusion and sacrifice. Urinary microalbumin?to?creatinine ratio (UACr), total cholesterol and triglyceride in kidney tissues were measured by ELISA. BODIPY 493/503 staining and standard transmission electron microscopy (TEM) of kidney tissues was performed for evaluating lipid accumulation and podocyte foot effacement in the kidney. Kidney tissues were also evaluated by PAS stain and TUNNEL stain. PCSK9, podocin and nephrin were quantified through real?time PCR, and the Bcl?2, Bax and cleaved caspase 3 were evaluated by Western blotting. Results Total cholesterol and triglyceride contents were higher in the kidneys of PCSK9 KO mice than controls (P<0.05). The level of lipid accumulation in glomeruli and tubules through BODIPY 493/503 stain, and the amount of lipid drop in TEM were more serious in PCSK9 KO mice. UACr and podocyte foot process effacement were increased, and the transcription of podocin and nephrin were decreased in the kidneys of PCSK9 KO mice (all P<0.05). The expression of Bcl?2 was decreased, and Bax and cleavedcaspase 3 were increased in the kidney samples of PCSK9 KO mice. Conclusion PCSK9 might be reversely involved in lipid homeostasis and accumulation, resulting in injury and apoptosis in the kidneys of C57BL/6 mice.

Objective:To analyze the research progress and hotspots on drug resistance of helicobacter pylori in China and abroad since 2000, in order to provide theoretical reference and basis for the study of digestive system diseases.Methods:The Chinese and English literature related to helicobacter pylori resistance, which were included in the Chinese National Knowledge Infrastructure (CNKI) database and the Web of Science database, were searched from 2000 to 2021. We imported the retrieved literature into Citespace6.1.R2 software, performed visual analysis on authors, countries and institutions, keywords, cited literature, and drew visual graphs.Results:A total of 2 824 Chinese literature and 1 885 English literature were included. The authors with the highest volume of publications in Chinese and English literature are Hu Fulian and Gisbert JP, respectively. The institutions with the highest volume of publications are the First School of Medicine, Beijing University and the Baylor School of Medicine in the United States. The keywords with high centrality in Chinese literature include clarithromycin, eradication rate, drug resistance, amoxicillin, metronidazole, etc. In the analysis of cited literature, it was observed that the Maastricht Consensus report holds an important position in this field.Conclusions:The use of Citespace visualization analysis has intuitively elucidated the research hotspots on the drug resistance of Helicobacter pylori.

Objective To evaluate the effect of clemastine fumarate on Toll-like receptor 4/phosphatidylinositol-3-kinase/serine-threonine kinase (TLR4/PI3K/Akt) signaling pathway during hypoxia-reoxygenation (H/R) in rat cardiomyocytes.Methods H9C2 cells of rats cultured in vitro were seeded in culture wells or dishes at a density of 1×105 cells/ml and divided into 3 groups (n=11 each) by using a random number table method:control group (group C),H/R group and clemastine fumarate group (CF group).Cardiomyocytes were exposed to 5％ CO2-95％ N2in a low-glucose DMEM medium at 37℃ for 4 h followed by 4 h reoxygenation.At 4 h of reoxygenation,the cell viability was detected by CCK-8 assay,the ultrastructure was observed with a transmission electron microscope,the expression of TLR4,PI3K,phosphorylated Akt (p-Akt) and caspase-3 was detected by Western blot,and the expression of TLR4,PI3K and caspase-3 was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the expression of TLR4 and caspase-3 was up-regulated,and the expression of PI3K and p-Akt was down-regulated in group H/R (P＜0.05).Compared with group H/R,the cell viability was significantly increased,the expression of TLR4 and caspase-3 was down-regulated,the expression of PI3K and p-Akt was up-regulated (P＜0.05),and the mitochondrial damage was significantly attenuated in group CF.Conclusion The mechanism by which clemastine fumarate alleviates H/R injury to rat cardiomyocytes may be related to inhibiting TLR4 expression and activating PI3K/Akt signaling pathway.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.