Objective To investigate dynamic metabolism in vivo of Ginkgo Folium Tablet under the guidance of sequential metabolism thoughts. Methods In situ closed-loop in rats was carried out to study sequential metabolism of Ginkgo Folium Tablet through oral digestive system, namely to investigate and compare the intestinal flora metabolism, the gut wall metabolism and hepatic metabolism, combined with chromatographic fingerprint of blood samples. Results The analysis showed that 12 peaks in Ginkgo Folium Tablet were metabolized by intestinal flora, and 7 peaks generated through the gut wall. Most components of Ginkgo Folium Tablet were metabolized in liver, and 3 original medicine components were directly into the blood. Conclusion This study conducts a qualitative description of metabolism of Ginkgo Folium Tablet in different parts of the oral route, and provides references for the quality control, mechanism explanation and secondary development for Ginkgo Folium Tablet.

Objective To investigate the relationship between smoking and insulin resistance in non-obese male patients with CAD. Methods 414 consecutive non-obese male patients with angiographically-documented CAD(luminal diameter narrowing>50%)were recruited,including 113 nonsmokers and 301 smokers.With 99 miht smokers(<400 packs/year),95 medium smokers(400-799 packs/year)and 107 heavy smokers(≥800 packs/year).Insulin resistance index(IRI)was expressed by homeostasis model assessment for insulin resistance(HOMA-IR)calculated by the formula of[fasting serum glucose(mmol/L)×fasting plasma insulin(mU/L)]/22.5.IRI≥2.69 was defined as insulin resistance,while IRI<2.69 was insulin sensitive.Fasting glucose,fasting insulin and IRI were recorded and odds ratio for the incidence of insulin resistance was calculated.Results Fasting glucose was higher in heavy smokers (5.86 mmol/L)than that in nonsmokers(5.51 mmol/L,P=0.037)and mild smokers(5.33 mmol/L,P=0.014).Fasting insulin and IRI were also significantly higher in heavy smokers(10.25 mU/L)than those in non-smokers(8.72 mU/L,P=0.0231,respectively)and mild smokers(8.67 mU/L,P=0.023 1).Compared with nonsmokers,the odds ratio for the incidence of insulin resistance was 1.53(95%CI 0.55-2.94;P=0.027)in medium smokers and 1.89(95%CI 0.49-3.14;P=0.018)in heavy smokers.Conclusions The relationship between smoking and insulin resistance is highly dose dependent in non-obese male patients with CAD.

Objective:To investigate the relationship between serum matrix metalloproteinase-9 (MMP-9) level and the location and severity of bleeding in patients with cerebral microbleeds(CMBs).Methods:A total of 60 CMBs patients admitted to the Department of Neurology of the First Affiliated Hospital of the Xinxiang Medical University from January 2019 to August 2020 were selected as subjects as the CMBs group, and 60 healthy controls without nervous system diseases in outpatient physical examination during the same period were selected as the control group. The clinical data and biochemical indicators of the two groups were collected. Serum MMP-9 levels were measured by enzyme linked immunosorbent assay (ELISA). According to susceptibility weighted imaging (SWI), CMBs patients were divided into grade 1 group ( n=24), grade 2 group ( n=19) and grade 3 group ( n=17), and according to the micro analytical rating scale (MARS), the CMBs patients were divided into the lobar group ( n=19), the deep or infratentorial group ( n=17) and the mixed group ( n=24).The relationship between serum MMP-9 level and the location and severity of CMBs was analyzed. SPSS 19.0 software was used for data statistical analysis.One-way ANOVA, t-test and rank sum test were used for comparison. Logistic regression analysis was used to analyze the influencing factors. Pearson correlation analysis and Spearman correlation analysis were used for correlation analysis. Results:The level of MMP-9 in CMBs group was significantly higher than that in control group (208.13(142.25, 285.88) μg/L, 149.50(93.40, 186.51)μg/L), and the difference was statistically significant ( P<0.05). Serum MMP-9 level was a risk factor of CMBs ( β=1.322, OR=3.750, 95% CI=2.038-7.997, P=0.002). The difference of level of MMP-9 in different severity of CMBs was statistically significant (147.55(109.25, 266.47)μg/L, 242.12(147.55, 288.80)μg/L, 270.42(203.43, 364.27)μg/L, P=0.017). Serum MMP-9 level was positively correlated with the number of CMBs ( r=0.371, P=0.003). The difference of MMP-9 level of CMBs in different locations were statistically significant (249.77(158.43, 338.46)μg/L, 188.83(138.52, 243.15)μg/L, 210.65(144.25, 255.78)μg/L, P=0.013). The increased serum MMP-9 level was a risk factor for CMBs( β=0.401, OR=1.122, 95% CI=1.004-1.204, P=0.036). Conclusion:The increased level of serum MMP-9 may be a risk factor of CMBs, especially for CMBs in cerebral lobesand, and the level of MMP-9 is positively correlated with the severity of CMBs.

According to different experimental methods of induced diabetic retinopathy (DR) and different characteristics of the observed retinopathy, DR animal models can be divided into drug or dietary-induced models, oxygen-induced retinopathy (OIR) models, spontaneous inheritance models, and transgenic models. At present, induced model is one of the most commonly used animal model for DR study, which has the advantages of short modeling cycle, low cost, simple experimental operation and good repeatability. However, the drugs have certain side effects on various organs of animals and the risk of animal death is higher. OIR model has good repeatability, good stability and relatively low cost. However, due to the lack of metabolic changes of hyperglycemia in OIR mice, this model cannot accurately reflect the effects of metabolism on retina under hyperglycemia. The pathological changes of the spontaneous model are relatively stable, however, the application of this model is limited because the genetic homogeneity of diabetes differs from that of human and the cost is high. Transgenic model has definite etiology, however, its application is limited owing to the high cost and the high requirements of technology, operation and equipment. Therefore, researchers should comprehensively consider characteristics and limitations of different models while choosing suitable DR model based on research objectives, observation indicators, experimental conditions, and funds. In addition, animal models that can more accurately simulate DR need to be developed to provide more effective tools for studying the mechanism of DR and developing feasible prevention and treatment approaches.

Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF) levels and white matter high signal and non-dementia vascular cognitive dysfunction in patients with cerebral small vascular disease (CSVD).Methods:Total 106 patients with CSVD who were admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical College from April 2019 to December 2020 were enrolled.They were divided into vascular cognitive impairment no dementia group (VCIND group, n=47) and no vascular cognitive impairment group (N-VCI group, n=59)according to mini-mental assessment scale (MMSE), Montreal cognitive assessment (MoCA) scale and activity of daily living scale (ADL). Serum VEGF levels were detected by enzyme-linked immunosorbent assay (ELISA). The baseline data, serum VEGF levels, MoCA score and Fazekas score were compared between the two groups.The correlation between serum VEGF level and white matter high signal and cognitive function was analyzed.SPSS 19.0 software was used for data processing.The statistical methods were t-test, Chi square test, nonparametric test, Logistic regression analysis, Pearson correlation analysis and Spearman correlation analysis. Results:There were significant differences in serum VEGF level((464.18±114.58)pg/mL, (414.17±45.80)pg/mL, F=22.880), MoCA score((13.07±6.48), (20.17±4.06), F=17.920) and Fazekas score (4(3, 5), 3(1, 3), Z=-4.189)between the two groups (all P<0.05). The level of VEGF( β=0.008, OR=1.008, 95% CI=1.001-1.015, P<0.05) was the influencing factor of cognitive function in patients with CSVD .The level of VEGF was negatively correlated with the total score of MoCA, attention and calculation power, and orientation ability ( r=-0.345, -0.373, -0.445, all P<0.05) and it was positively correlated with the total Fazekas score and the Fazekas score of paraventricular and deep white matter ( r=0.392, 0.495, 0.302, all P<0.05). There was a linear trend between the high signal grade of paraventricular and deep white matter and VCIND (both P<0.05). Conclusion:Serum VEGF level is correlated with cognitive function and white matter hyperintensity in patients with CSVD.The increase of VEGF level may be a factor reflecting cognitive dysfunction.In addition, with the increase of white matter hyperintensity level, the risk of VCIND in CSVD is increased.

Objective:To investigate the relationship between serum glial cell line-derived neurotrophic factor (GDNF) levels and neuroimaging changes and cognitive impairment in patients with cerebral small vascular disease (CSVD).Methods:135 patients with CSVD recruited from the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from September 2021 to July 2022 were assessed by cranial multimodal magnetic resonance imaging and Montreal cognitive function assessment (MoCA), and the basic data were analyzed at the same time.The serum GDNF concentration of all patients was detected by enzyme-linked immunosorbent assay (ELISA). According to the median GDNF concentration, the patients were divided into low GDNF group and high GDNF group. The baseline data, MoCA score and imaging markers of the two groups were compared by Mann-Whitney U test, chi-square test, logistic regression, Kruskal-Wallis H test and Jonckheere-Terpstra trend test, and the correlation between serum GDNF level and imaging markers and cognitive function of patients with CSVD was analyzed. Results:The median serum GDNF concentration of all CSVD patients was 16.66 pg/mL. Multivariate logistic regression analysis showed that low serum GDNF level was a risk factor for white matter hyperintensity and total image load in patients with CSVD. Serum GDNF level was a protective factor of cognitive impairment in patients with CSVD in multiple logistic regression analysis. The area under the curve of ROC curve analysis of cognitive impairment after CSVD predicted by serum GDNF level was 0.735, the sensitivity was 66.4%, and the specificity was 71.4%. The level of serum GDNF was positively related with visual space and executive function, attention and computational power, delayed recall and orientation( r=0.267, 0.187, 0.219, 0.215, all P<0.05). Conclusion:The serum GDNF level is related to white matter hyperintensities, total imaging load and cognitive impairment in patients with CSVD. Serum GDNF level may play a predictive role in CSVD and cognitive impairment.