Objective To investigate the changes and potential roles of the expression of apoptosis signal-regulating kinase 1(ASK1),thioredoxin(Trx)and thioredoxin reductase(TrxR)in the pathogenesis of lung injury of premature newborn rats exposed to hyperoxia. Methods In the first day after delivery,preterm SD rats were randomly divided into air group and hyperoxia group with 64 rats in each.The rats were respectively sacrificed at 1,4,7,10 and 14 days after air or hyperoxia exposure.Sections of 1ungs were stained with HE to observe the histologic changes.Trx and TrxR mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Immunohistochemistry was used to detect the expression and distribution of ASK1.Western blot was used to detect the expression of ASK1 protein. Results Rats in hyperoxia group showed typical lung injury,which was characterized by alveolitis and delayed of lung development.Immunohistochemistry detected that ASK1 expressed generally in the cytoplasm of both alveolar epithelial cells and vascular endothelial cells:ASK1 protein expression in hyperoxia group at 1th and 4th day were 0.4382±0.0227 and 0.5270±0.0432,higher than in the air group(0.3458±0.0263 and 0.3760±0.0058)(P<0.01),and it was until 7th day that the expression became weaker(0.4343±0.0254),but still higher compared with the air group(0.3473±0.0220)(P<0.01).Compared with the air group,Trx and TrxR mRNA of the hyperoxia group increased significantly and peaked at lOth day(0.6860±0.0811)and 7th day(2.0351±0.1600),respectively(P<0.05).ASK1 protein expressions resulting

Objective To explore the effects of expression of thioredoxin-2(Trx-2) suppressed by small interference RNA(SiRNA) in A549 cells exposed to hyperoxia on expression of nicotinamide adenine dinucleotide(NADH) dehydrogenase subunit 1(ND1)and cytochrome C oxidase Ⅰ(COX Ⅰ). Methods A549 cells were gained by serial subcultivation in vitro and transfered with synthetic Trx-2 sequence-specific SiRNA and then were randomly divided into air group without interference,hyperoxia group without interference,air group after interference,and hyperoxia group after interference.After exposure to oxygen or room air for 12,24 and 48 h,expressions of Trx-2,ND1 and COX Ⅰ mRNA of these cells were detected by reverse transcription-polymerase chain reaction (RT-PCR),and Trx-2 protein was detected by Western blot. Results (1)Sequence-specific SiRNAtargeting Trx-2 could significantly down-regulate its expression in A549 cells.(2)Trx-2 mRNA levds inhyperoxia group without interference at 24 h was higher than those in air group without interference(0.7799±0.1249 VS 0.4424±Ⅰ.1140,P<0.05).Th-2 mRNA levels in hyperoxia group after ireedcrence at 24 hand 48 h were 0.2774±0.0174 and 0.2587±0.0069,lower than those in air group after interference andhyperoxia group without interference (P<0.05).(3)ND1 mRNA levels in hyperoxia group without interference at 24 h was 0.6609±0.0368,lower than those in air group without interference(0.8898±0.1049)(P<0.05).ND1 mRNA levels in hyperoxia group after interference at 12 h was 0.8848±0.0135,higher than those in air group after imederence(P<0.05).ND1 mRNA levels in hypemxia group afterinterference at 48 h was 0.3808±0.0937,lower than those in air group after imerference and hyperoxiagroup without interference(P<0.05).(4)COXI mRNA levels in hypemxia group without inteference at 12,24 and 48 h were 1.7313±0.4331,2.1929±0.6722 and 2.0754±0.2584,higher than those in air group witheUt interference,respectively (P<0.05). Conclusions ND1 and COXⅠ participate in thedevelopment of hyperoxia indUCed lung.injury,and Trx-2 is likely to have protective effect on mitochondria ofA549 cells in hyperoxia lung injury.

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.

OBJECTIVESTo compare primary stenting in the infarct-related coronary artery with intravenous rt-PA therapy plus rescue intracoronary stenting.

METHODSNinety-eight patients with a first acute myocardial infarction (AMI) were randomly treated with primary intracoronary stenting (primary stenting group) or with intravenous rt-PA therapy plus rescue intracoronary stenting (thrombolysis plus stenting group). Thrombolysis in myocardial infarction (TIMI) flow grade was assessed by angiography in emergency, and cardiac function (left ventricular ejection fraction, LVEF) was calculated by echocardiography before discharge between the two groups.

RESULTSThere were 47 patients (97.91%) in primary stenting group and 50 patients (100%) in thrombolysis plus stenting group had achieved TIMI grade 2 - 3 flow after the procedure. But the former had more cases (93.8%) of TIMI 3 flow than that of latter (60.0%, P = 0.0001). There was no difference between the two groups in cardiac events during hospitalization. But the patients in primary stenting group had better cardiac function (LVEF 0.62 +/- 0.14 vs. 0.50 +/- 0.12, respectively, P = 0.0001) between the two groups.

CONCLUSIONSPrimary intracoronary stenting may improve myocardial reperfusion in emergency and inhibit the decline of cardiac function after AMI in comparison with intravenous rt-PA thrombolysis plus rescue intracoronary stenting.

Aged ; Angioplasty, Balloon, Coronary ; Combined Modality Therapy ; Creatine Kinase ; blood ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Infusions, Intravenous ; Isoenzymes ; blood ; Male ; Middle Aged ; Myocardial Infarction ; blood ; physiopathology ; therapy ; Recombinant Proteins ; therapeutic use ; Stents ; Tissue Plasminogen Activator ; therapeutic use ; Treatment Outcome

Objective To clarify the role of insulin resistance on spontaneous recanalization of infarct-relat-ed arteries in the early phase of acute ST-elevation myocardial infarction (STEMI) in patients with normal glucose tolerance. Methods 141 consecutive patients with normal glucose tolerance and acute STEMI were enrolled in our study. Subjects were divided into TIMI 0-1 group (n =91 ) and TIMI 2-3 group (n =50) by primary coronary angi-ngraphy (CAG). The Gemini score and 0-3-vessel disease score estimated the severity and extent of coronary artery disease (CAD). Metabolic parameters and homeostasis model assessment for insulin resistance (IRI) were deter-mined. Results Serum level of fasting insulin, IRI and Gemini score were higher in TIMI 0-1 group than in TIMI 2-3 group [ (11.52±6.22)mU/L vs (7.54±3.65)mU/l,(2.79±2.32) vs (1.73±1.26),(59.17±26.95) vs ( 38.46±22.74) ( P <0.01)]. IRI was positively associated with Gemini score (r=0.185,P <0.05 ). Multivariate Logistic regression analysis revealed that IRI was independent risk factor influencing spontaneous recanalization of in-farct-related urteries(OR=2.87,95% CI=1.09-7.57,P<0.05). Conclusion Insulin resistance is independent risk factor influencing spontaneous recanalizafion of infarct-related arteries in the early phase of acute STEMI in pa-tients with normal glucose tolerance.

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. Materials and Methods: IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. Results: We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. Conclusion These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. Materials and Methods: IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation. Results: We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. Conclusion These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

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.

BACKGROUND: Interleukin-1 is an important pro-inflammatory cytokine that has been documented in the regulation of bone inflammation and bone remodeling. A previous study has demonstrated that interleukin-1α can induce apoptosis while inhibiting osteoblast differentiation in MC3T3-E1 cells. OBJECTIVE: To investigate the role and mechanism of interleukin-1α on osteoclast activation and bone loss in mice. METHODS: (1) Cell test: RAW264.7 cells were either treated with interleukin-1α alone or with receptor activator of nuclear factor-κB ligand (RANKL) for 1 and 4 days. Cell viability was tested by cell counting kit-8 assay. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The mRNA and protein levels of osteoclast-specific genes and genes related to nuclear factor-κB pathway and Wnt/β-catenin pathway were tested by real-time fluorescence quantitative PCR, immunofluorescence staining or western blot. Bone marrow-derived macrophages were either treated with interleukin-1α alone or with RANKL and macrophage colony-stimulating factor for 7 days. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The protein levels of osteoclast-specific genes were tested by western blot. (2) Animal test: Twenty-four male C57BL/6J mice (6-8 weeks old) were assigned into two groups at random: control group and test group. Mice were subsequently treated with interleukin-1α solution or PBS by intraperitoneal injection twice a week for 5 weeks. Bone tissues from the femurs were performed with micro-computed tomography analysis and hematoxylin-eosin staining, tartrate resistant acid phosphatase, and immunofluorescence analysis. RESULTS AND CONCLUSION: Cell test: Interleukin-1α alone significantly increased RAW264.7 cell proliferation, but stimulated cell differentiation into osteoclasts in combination with RANKL (P < 0.05). Interleukin-1α significantly increased the expression of osteoclast-related markers and the number of tartrate resistant acid phosphatase-positive multinuclear cells in RAW264.7 cells and bone marrow-derived macrophages in the existence of RANKL or RANKL+macrophage colony-stimulating factor (both P < 0.05). Interleukin-1α was found to significantly enhance the nuclear factor-κB and Wnt/beta-catenin signaling in RAW264.7 cells (P < 0.05). Blocking of nuclear factor-κB or Wnt3 signaling not only reversed the activation of nuclear factor-κB and Wnt3 signaling but also weakened the enhanced expression of osteoclast-specific genes induced by interleukin-1α in RAW264.7 cells (P < 0.05). Animal test: interleukin-1α induced bone loss in mice while also upregulating the expression of osteoclast-specific markers, RANK, TRAF6 and p65, and Wnt3 in vivo (P < 0.05). The findings indicate that interleukin-1α can induce osteoclast activation and bone loss by promoting the nuclear factor-κB and Wnt signaling pathways.

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.