In order to show the development situation and trend in plaque research, Thomson Innovation Platform-covered application of patents associated with plaque researches was quantitatively analyzed using the Thomson Data Analyzer and Thomson Innovation or other tools, which revealed the overall development situation, the main accepted countries, the main application institutions and the technological direction layout of patents associated with plaque researches.

The current situation of medical information was analyzed by displaying the co-appearance of countries and time, top 5 journals and co-appearance of subject headings in papers on medical information published in 1995-2014 with the papers on medical informatics covered in ISI Web of Science Database as an sample , in order to promote the study and provide reference for the related persons and institutions .

OBJECTIVE To establish an in vitro test method and to evaluate the genotoxicity of chemicals using primary cultured mouse hepatocytes and the changes in phosphorylated histone H2AX(γH2AX)expression levels to provide a more reliable marker of the identification of genotoxicity. METHODS Hepatocytes were isolated from BALB/c mice by an improved two-step collagenase diges?tion method and then cultured in sandwich configuration. The primary cultured hepatocytes were treat?ed with various concentrations of four known genotoxic agents bleomycin(BLM),benzo(a)pyrene〔B (a)p〕,styrene and styrene-7,8-oxide(SO)within the range of 40 μmol · L-1 and two non-genotoxic agents azathioprine(Aza)and ciclosporin A(CsA)at different time points within 24 h. The cytotoxicity induced by these toxicants was assessed by CCK-8 assay. Then,the changes in γH2AX expression levels in treated cells were determined by flow cytometry. RESULTS The four genotoxic agents could be detected and two non-genotoxic agents could not be detected by this method. The γH2AX expression level was the highest when hepatocytes were exposed to BLM and SO for 3 h,or B(a)p and styrene for 6 h(P<0.01). The production of γH2AX was 25.67,18.36,12.43 and 14.25 for the four types of genotoxic agents,respectively,and was approximately 19,13,9 and 11 times that of the vehicle control group(P<0.01)at the optimum time point and concentration. There was a significant positive corre?lation between the indicated concentrations of genotoxic chemicals and γH2AX expression levels(P<0.01). In addition,the production ofγH2AX indicated no marked increase in two non-genotoxic agents such as Aza and CsA in comparison with the control group. CONCLUSION This test method can effec?tively distinguish genotoxic agents from non-genotoxic agents,and direct genotoxic agents from indirect genotoxic agents in the absence of S9. γH2AX might be a reliable marker for the identification of the potential genotoxicity of chemicals.

Objective To analyze the institutional cooperation networks of 137 military hospitals in terms of published papers, trends of cooperation and co-authorship in order to guide the cooperation between military hospitals.Methods The institutional cooperation, co-authorship, author-keyword co-occurrence and author-subject co-occurrence in the 137 military hospitals were analyzed with the Thomson data analyzer( TDA) software.Results and Conclusion The institutional coop-eration between military hospitals could be divided into 5 types and were based on the principle of proximity of locations and similiarity of research.The cooperaiton circle with Chinese PLA General Hospital as the center was expanded over time. The institutional cooperation between military and civilian hospitals was also based on the principle of proximity of locations and similiarity of research.Cooperation between productive authors mainly occurred in the same research group but co-au-thorship outside the research group was scarce.The potential competition or cooperation between research fields and authors can be analyzed by comparing co-authorship and author-keyword co-occurrence.

Objective To construct erythromycin-overproducing mutants by tandemly expressing S-adenosylmethionine synthetase gene metK, Vitreoscilla hemoglobin gene vhbS and pleiotropic regulatory gene adpA in Saccharopolyspora eryth-raea.Methods Through PEG-mediated protoplast transformation , the integrative plasmid carrying metK, vhbS and adpA was respectively introduced into erythromycin-producing wild-type strain S.erythraea A226 and industrial strain WB .The engineered strains were generated by apramycin resistance screening and PCR identification .The erythromycin production was compared in original strains and their mutants by the inhibition test of Bacillus subtilis and HPLC analysis .Results and Conclusion Four A226-derived mutants A226-P1-P4 and three WB-derived mutants WB-P1-P3 were independently obtained.Compared with wild-type strain A226, the relative erythromycin titer of the four engineered strains A 226-P1-P4 was increased from 8%to 25%by scoring the growth-inhibition zones .Further HPLC analysis showed that the four mutants had increased erythromycin A yield by 64%-94%.Likewise, the relative erythromycin titer and erythromycin A yield of the three engineered strains WB-P1-P3 were enhanced by 6%-10%and 31%-62%, respectively, in comparison with the original strain WB.The results show the universality of enhancing erythromycin productionvia tandem expression of metK, vhbS and adpA in S.erythraea.

Objective: To study the different ischemic characteristics of cerebral gray matter and deep white matter in patients with chronic cerebral artery severe stenosis or occlusion. Methods: A retrospective study was conducted on 30 patients with chronic unilateral cerebral artery severe stenosis or occlusion from April 2014 to April 2018 in our hospital. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time of peak time (TTP) and time to delay(TTD) of cerebral cortex gray matter and deep white matter in the blood supply area of the responsible artery (the affected side) and the contralateral hemisphere (the healthy side) were measured. Statistical analysis of the perfusion parameters of cerebral cortex gray matter and deep white matter in the affected side and contralateral side were performed using SPSS13.0 software package. T test was used for variance homogeneity, and t′ test was used for variance discrepancy, and P<0.05 was statistically significant. Results: The average values of CBF and CBV of the ipsilateral and contralateral cerebral cortex were increased than those of ipsilateral and contralateral cerebral deep white matter respectively(P<0.01). MTT, TTP and TTD of the ipsilateral and contralateral cerebral cortex were decreased than that of ipsilateral and contralateral cerebral deep white matter (P<0.01); CBF of ipsilateral cerebral cortex and CBV of ipsilateral cerebral deep white matter were not different from those of the contralateral cerebral cortex and deep white matter respectively, but CBF of ipsilateral cerebral deep white matter is decreased than that of the contralateral deep white matter (P<0.01). CBV of ipsilateral cerebral cortex is increased than that of the contralateral cerebral cortex (P<0.01). MTT, TTP and TTD of ipsilateral cerebral cortex and deep white matter were increased than those of contralateral cerebral cortex and deep white matter respectively(P<0.01). Conclusion Deep cerebral white matter perfusion decreased more significantly than cortical gray matter in the supply region of chronic cerebral artery severe stenosis or occlusion. CT perfusion imaging can quantify the degree of chronic cerebral ischemia and can provide quantitative diagnostic information for clinical treatment and efficacy evaluation.

OBJECTIVE:To study the improvement effects of citalopram combined with huperzine A in aged depression model rats. METHODS:Aged rats were randomly divided into blank control group,model group,huperzine A group(0.3 mg/kg),citalo-pram group(5 mg/kg),and combination group(huperzine A 0.3 mg/kg+citalopram 5 mg/kg),10 in each group. Except for blank control group,rats in other groups received chronic unpredictable mild stress to reduce depression model. After modeling,rats were intragastrically administrated relevant drugs once a day,for 2 weeks. The depression,learning and memory behavior changes of rats in each group were observed by using open-field test,sucrose consumption test,tail suspension test,forced swimming test and Morris water maze test. RESULTS:Compared with blank control group,the horizontal crossing number,uprightness number,su-crose preference rate,crossing number in platform,percentages of target quadrant distance and time of rats in model group were ob-viously decreased (P<0.05 or P<0.01);immobility time of tail suspension and swimming,escape latency were obviously pro-longed(P<0.05 or P<0.01). Compared with model group,the depression-related indexes of rats in citalopram group and combina-tion group were obviously improved(P<0.05 or P<0.01),and combination group had better effects;the learning and memory-re-lated indexes in combination group were obviously improved(P<0.05 or P<0.01),only crossing time in platform in huperzine A group and citalopram group were obviously increased (P<0.05 or P<0.01),and other learning and memory-related indexes had no obvious changes(P>0.05). CONCLUSIONS:Citalopram combined with huperzine A can obviously improve the depression be-havior,learning and memory ability of aged rats with depression,showing better effects than citalopram alone.

Objective To explore the predictive value of short term cognitive assessment in the acute phase of ischemic stroke for 3-6 months after stroke.Methods The demographic data,vascular risk factors,clinical and imaging data of 254 patients with acute ischemic stroke from August 2016 to December 2017 were prospectively registered.The cognitive function was assessed by Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) 3 weeks after stroke onset.Comprehensive cognitive function assessment was performed after 3-6 months of stroke.Multiple factor Logistic regression was used to screen the independent risk factors of cognitive domain and overall cognitive function in 3-6 months.Results Totally 254 consecutive patients with acute ischemic stroke were enrolled.Combined with the inclusion and exclusion criteria,161 patients completed the baseline cognitive assessment,and 138 completed the comprehensive cognitive assessment in 3-6 months after stroke.Logistic regression analysis showed that 3 weeks baseline cognitive status was an independent factor affecting memory (P＜0.05,OR =62.47,95％CI=13.00-205.00),execution (P＜0.05,OR=38.29,95％CI=8.00-170.00),language (P＜0.05,OR=6.46,95％CI=2.31-18.04) and information processing speed (P＜0.05,OR=5.88,95％CI=2.24-15.41) in 3-6 months after stroke.According to the number of impaired cognitive domains,the overall cognitive function was defined.There were 61 cases of no or mild cognitive dysfunction group and 77 cases of moderate or severe cognitive impairment group.Multifactor logistic analysis showed that baseline cognitive status was independent of the overall cognitive function of 3-6 months after apoplexy adjusting for the age and education level (P＜0.05,OR=25.32,95％ CI =7.52-85.39).Conclusion Short cognitive assessment in early apoplexy can predict the short-term functional status of cognitive domains such as memory,execution,language and information processing speed after stroke,and can also predict the overall cognitive level.

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.

Objective To investigate anti-hypoxia activity and protective effects of Lishukang capsule on rat brain tissue at simulated high altitude hypoxia.Methods The anti-hypoxic activity of Lishukang capsule was evaluated with normobaric hypoxia test and acute hypobaric hypoxia test in mice.In addition,rats were exposed to large hypobaric hypoxia chamber stim-ulating 8 000 m altitude.The pathological changes of rat brain tissue before and after hypoxia were observed.The oxidative stress indicators and metabolism parameters in brain were measured.Results The low,medium and high Lishukang doses can effectively prolong the survival time of mice(P<0.01)in the dose dependent manner.The medium and high Lishukang doses were significantly better than those of Rhodiola rosea capsules(P<0.05 or P<0.01).The low,medium,high Lishukang dose groups reduced the mortality of acute hypobaric hypoxia mice(P<0.01)with dose dependent effects.The mice mortality in medium and high dose groups was lower than that of Rhodiola rosea group(P< 0.01).Compared with normal control group,the hypoxic model rats exhibited pathological injury in the brain tissue after exposure to hypobaric hypoxia stimulating 8 000 m altitude.The contents of MDA,H2O2,NO,LD and LDH activity increased significantly(P<0.05 or P<0.01), while the activities of SOD,CAT,GPX were significantly decreased(P<0.05 or P<0.01).After pretreatment with Lishu-kang capsule,the pathological damage of rat brain tissue was alleviated and the content of MDA,NO in the brain tissue was re-duced(P<0.05 or P<0.01).The levels of H2O2,LD content and LDH activity in medium and high dose groups were signifi-cantly decreased(P<0.05 or P<0.01).The activities of SOD,CAT and GPX in high dose group were significantly increased(P<0.05).Conclusion Lishukang capsule has good anti-hypoxia activity.It provides protective effect for the injuries induced by hypobaric hypoxia in rats.The mechanism may related to the improvement of antioxidant capability,reduction of free radical damage and amelioration of energy metabolism.