Objective To research the applications of resting-state functional MRI in conjunction with voxel-based morphometry on cerebral functions and structures in patients with schizophrenia. Methods Thirty-two patients with schizophrenia and 32 healthy people underwent resting state functional magnetic resonance imaging (Rs-fMRI)and sagittal scanning T1WI with 3D FFE Pulse Sequence. Rest1.8 software was applied to calculate the differences of amplitude of standardized low-frequency fluctuation(ALFF)between the two groups,then the voxel-based morphometry(VBM)data of abnormal brain regions were evaluated to compare the differences of grey matter intensity. Finally,combining with ALEF and VBM,we explored the changes of cerebral functions and structures. Results As compared to the control group ,the ALFF-elevated regions were the right putamen ,the left orbital frontal cortex extending to the left putamen and left dorsal-lateral superior frontal gyrus;the ALFF-decreased regions were the right inferior tempotalgyrus,the left posterior cingulated gyrus and the left angular gyrus(P<0.05). No elevated regions of grey matter intensity were found in the patient group. Conclusions Extensive abnormal active regions of the brain under resting state could be found in patients with schizophrenia ,the grey matter intensity of abnormal regions also decreased generally. They are in accordance with the glutamate-hypothesis of schizophrenia ,which involves extensive impairments of neurons ,disorders of neurotransmitter′s circulations and balances.

Because of the high morbidity and mortality rate,cardio-cerebrovascular diseases,including cerebral embolism, cerebral hemorrhage,cerebral vasospasm and myocardial infarction,have become main diseases threatening human health. Tradition-al chinese medicine(TCM)holds that the basic pathogenesis is Qi imbalances,which could be improved by benefiting Qi and promot-ing blood circulation. The compatibility of Radix astragali and Radix salviae miltiorrhiae are particularly suitable for treating the car-dio-cerebrovascular system diseases by improving Qi deficiency and blood stasis. This paper focuses on the application of Radix astrag-ali,Radix s. miltiorrhiae and their compatibility for treating the cardio-cerebrovascular system diseases. Moreover,our research would offer valuable references for the development of new drugs related to the treatment of cardio-cerebrovascular system diseases.

AIM:To investigate the effect of quercetin on the biological functions of rat bone marrow-derived endothelial progenitor cells (EPCs) and its potential mechanisms.METHODS:The bone marrow-derived mononuclear cells of Sprague-Dawley rats were isolated by density gradient centrifugation.The differentiated EPCs were cultured specially and stained with DiI-Ac-LDL and FITC-UEA-1.CD133+ and FLK-1+ were detected on the cell surfaces.After 14 d, the EPCs were incubated with a PI3K inhibitor BYL719 (3 μmol/L) and an ERK inhibitor FR180204 (15 μmol/L).After incubation of the inhibitors for 2 h, the cells were treated with quercetin at different concentrations (0, 10, 20, 40, 80 and 100 μmol/L).MTT assay and Transwell assay were used to detect cell viability and the number of migratory cells.The protein levels of AKT, eNOS, ERK and their phosphorylated status were determined by Western blot.RESULTS:Quercetin enhanced the viability and migration of the EPCs at a dose-dependent manner.However, the PI3K inhibitor BYL719 suppressed the QUE-induced cell viability and migration.Moreover, ERK inhibitor FR180204 exerted the similar inhibitory effect on the cell viability but had no effect on cell migration.Quercetin activated the phosphorylation of AKT, eNOS and ERK.On the other hand, BYL719 was observed to inhibit the phosphorylation of AKT and ERK.FR180204, however, was showed to inhibit the phosphorylation of ERK only.On the contrast, the stimulatory effects that quercetin exerted on the expression of eNOS and its phosphorylation were suppressed by BYL719 and FR180204.CONCLUSION:Quercetin stimulates the viability and migration of EPCs via PI3K/AKT/eNOS and ERK/eNOS signaling pathway, which would be beneficial for cardiovascular health.

[ ABSTRACT] AIM:To observe the influences of different concentrations of MG132 on apoptosis and beta-amyloid protein ( Aβ) generation in SH-SY5Y cells, and to explore the underlying mechanism.METHODS:SHSY-5Y cells were incubated with MG132 for 24 h.The final concentrations of MG132 were 2.5, 5 and 10μmol/L.The cell viability was de-termined by MTT assay.The cell apoptosis was assessed by flow cytometry.The levels of Aβwere measured by ELISA. The relative protein levels were detected by Western blot.RESULTS:In the SH-SY5Y cells, MG132 reduced the cell via-bility, induced the cell apoptosis, increased the level of Aβ, and increased the expression of the related proteins for Aβgeneration in a concentration-dependent manner.CONCLUSION: MG132 induces apoptosis and increases the levels of Aβ1-42 and Aβ1-40 by regulating the proteins related to Aβgeneration in the SH-SY5Y cells.

Objective To investigate the effects of age and gender on anti-oxidative,antiinflammatory and anti-apoptosis functions of high-density lipoprotein (HDL).Methods Totally 120 healthy subjects aged from 20 to 60 years were randomly divided into young and middle-aged male (n=60) group and female (n =60) group,and the 120 healthy elderly aged from 60 to 78 years divided into elderly male (n =60) and elderly female (n =60) groups.Serum levels of high-and low-density lipoprotein cholesterol (HDL-C,LDL-C),total cholesterol (TC),and triacylglycerol (TG) were detected.Content of malonaldehyde (MDA) was detected to determine anti-oxidative function of HDL.Adhesion assay of endothelial cells and monocytes (THP1) was adopted to test the protective effects of HDL on endothelial cells.The expressions of endothelial cell adhesion molecules,VCAM-1 and ICAM-1,were analyzed by Western blot.MTT and flow cytometry assays were used to detect the viability and apoptosis of the cells to test anti-apoptosis function of HDL.Results The levels of low-density lipoprotein,triglycerides and total cholesterol were higher in elder female group than in other three groups (all P＜0.05).The level of HDL-C was higher in young and middle-aged females than in other three groups(all P＜0.05).The level of MDA was higher in elder female group than in other three groups(all P＜0.05).The level of MDA was higher in elder male group than in the young and middle-aged male and female groups(all P＜0.05).After protection of HDL,the number of monocytes adhesion and expression levels of VCAM-1 and ICAM-1 were higher in elder groups than in young and middle-aged male and female groups(all P＜ 0.05).Relative survival and viability rates of endothelial cells were higher in young and middle-aged groups than in elder groups (all P＜0.05).Conclusions Ageing in both male and female induces impairments of anti-oxidative,anti-inflammatory and anti-apoptosis functions of HDL,with more evident decrease in anti-oxidative function in females.

[ABSTRACT]AIM:Toinvestigatetheinteractionandthemechanismofsphingosine-1-phosphate(S1P)and phospholipid transfer protein (PLTP) in lipoprotein.METHODS:The S1P content in the plasma and lipoprotein from 10-week-old PLTP transgenic (PLTP-Tg) mice and wild-type (WT) mice (n=8 each) was assayed.The transport of S1P by PLTP was determined by S1P transfer assay.The content of specific S1P carrier, apolipoprotein M, was detected by West-ern blotting.RESULTS:Plasma S1P contents were decreased by 21.1%in PLTP-Tg mice compared with WT mice.S1P content in high-density lipoprotein ( HDL) fraction ( HDL-S1P) from PLTP-Tg mice was decreased by 35.1% compared with WT mice, whereas the S1P in low-density lipoprotein (LDL) fraction (LDL-S1P) was increased by 127.4%.The re-sults of S1P transfer assay indicated that PLTP facilitated S 1P transport from erythrocyte to recombinant liposome at 37℃in D-Hanks buffer solution .The plasma content of apolipoprotein M was not changed in PLTP-Tg mice compared with WT mice.CONCLUSION:PLTP is a key factor to maintain plasma HDL-S1P under physical condition .Overexpression of PLTP decreases the HDL-S1P but increases LDL-S1P.The mechanism might be related to the capability of PLTP on trans-ferring S1P from erythrocyte to lipoprotein.

AIM:To investigate the inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on the scaven-ger receptor A1 ( SR-A1 ) in macrophage-derived foam cells induced by oxidized low-density lipoprotein ( ox-LDL ) . METHODS:RAW264.7 cells were pretreated with different concentrations (12.5, 25 and 50 mg/L) of D-4F or 50 mg/L inactive control peptide scrambled D-4F (sD-4F) for 1 h or endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyr-ic acid (5 mmol/L) for 30 min, followed by the treatment with 100 mg/L ox-LDL for 12 h.In addition, the cells were pre-treated with 50 mg/L D-4F or sD-4F for 1 h, and then stimulated with 2 mg/L tunicamycin (TM;an ERS inducer), for 4 h.The viability of the cells was measured by MTT assay, and the content of intracellular total cholesterol ( TC) was meas-ured by a tissue/cell TC assay.The protein and mRNA levels of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blotting and quantitative real-time PCR, respectively.The fluorescence intensity of DiI-ox-LDL in the cells was detected by a multifunctional microplate reader.RESULTS:D-4F significantly reduced ox-LDL-induced macro-phage injury and intracellular cholesterol accumulation, and attenuated the ox-LDL-induced expression of SRA1 and GRP78 in a dose-dependent manner.Additionally, D-4F significantly inhibited the TM-induced protein expression of SR-A1 and GRP78, and attenuated the uptake of ox-LDL by macrophages.CONCLUSION: D-4F reduces ox-LDL-induced macro-phage cholesterol accumulation and injury by inhibiting SR-A1 expression.The mechanism may be related to the inhibition of ERS signaling pathway mediated by GRP78.

Objective:To investigate the effect of microRNA-124 (miR-124) expression on pathological changes of Tau in elderly patients with Alzheimer disease to provide a new target for early detection and early treatment of Alzheimer disease in the elderly.Methods:The serum of 50 patients with Alzheimer disease from June 2017 to June 2018 in the Third People′s Hospital of Qinghai Province Hospital was taken as the sample of the research group and the serum of 50 healthy people was taken as the control sample. The mRNA expression of miR-124 in serum was determined by real-time polymerase chain reaction. The double antibody sandwich enzyme-linked immunosorbent assay was used. The expression levels of Tau protein and phosphorylated Tau (PTau) protein (S396, T181 and T231) were examined; pathological changes of Tau protein were detected by positron emission tomography.Results:The mRNA expression of serum miR-124 in Alzheimer disease patients was significantly higher than that in the control group (6.91 ± 0.41 vs. 5.11 ± 0.37, P < 0.01). The expression levels of total Tau protein, PTau (S396) protein and PTau (T181) protein in Alzheimer disease patients was significantly up-regulated, compared with those of the control group: (195.16 ± 20.48) ng/L vs. (123.25 ± 20.26) ng/L, (69.35 ± 8.92) ng/L vs. (40.53 ± 4.36) ng/L, (66.83 ± 8.45) ng/L vs. (35.87 ± 2.18) ng/L, P < 0.05. The pathological changes of Tau protein were clinically manifested as brain deposition, and the main parts were frontal lobe, occipital lobe, parietal lobe and temporal lobe. The overexpression of miR-124 was positively correlated with high expression of PTau (S396), high expression of PTau (T181) and high expression of total Tau, and it was an independent influencing factor. Conclusions:Overexpression of miR-124 can promote the expression of total Tau protein and phosphorylation of Tau protein, which is clinically indicative of Tau protein deposition in the brain of Alzheimer disease patients. It is expected to be a prognostic biomarker for Alzheimer disease.

Objective To analyze the distribution and antimicrobial resistance profile of clinical bacterial strains isolated from blood culture in China.Methods Clinical bacterial strains isolated from blood culture from participating hospitals of Blood Bacterial Resistance Investigation Collaborative System (BRICS) during January 2014 to December 2015 were collected.Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods as recommended by US Clinical and Laboratory Standards Institute(CLSI)2018.The data were analyzed with Whonet 5.6 software.Results During the study period,4 801 clinical bacterial isolates were collected from 26 hospitals,of which 1 798 (37.5％) were Gram-positive bacteria and 3 003 (62.5％) were gram-negative bacteria.The top 10 isolates were Escherichia coli (33.8％),coagulase-negative Staphylococcus (19.0％),Klebsiella pneumoniae (11.9％),Staphylococcus aureus (10.1％),Acinetobacter baumannii (4.0％),Pseudomonas aeruginosa (3.8％),Streptococcus (3.0％),Enterobacter sulcus (2.9％),Enterococcus faecium (2.8％) and Enterococcus faecalis (1.8％).Methicillin-resistant Staphylococcus aureus (MRSA) and methicillinresistant coagulase-negative Staphylococcus (MRCNS) accounted for 33.9％ (165/487) and 56.9％ (520/913) of Staphylococcus aureus and coagulase-negative Staphylococcus respectively.No vancomycinresistant Staphylococcus was detected.The resistance rate of Enterococcus faecium to vancomycin was 0.7％ (1/135),and no vancomycin-resistant Enterococcus faecaliss was detected.The positive rates of extendedspectrum β-1actamases(ESBLs)-producing Escherichia coli,Klebsiella pneumoniae and Proteus were 56.9％ (923/1 621),30.1％ (172/572) and 29.2％ (7/24),respectively.The positive rates of carbapenemresistant Escherichia coli,Klebsiella pneumoniae,Enterobacter,Salmonella and Citrobacter were 1.2％ (20/1 621),7.2％ (41/572),4.3％ (6/141),1.5％ (1/67) and 2.9％ (1/34),respectively.The resistance rates of Acinetobacter baumannii to polymyxin and tegacycline were 2.6％ (5/190) and 8.9％ (17/190)respectively,and that of Pseudomonas aeruginosa to polymyxin and fosfomycin were 1.1％ (2/183)and 0.6％ (1/183),respectively.Conclusions The surveillance results from 2014 to 2015 show that the main pathogens of blood stream infection in China are Gram-negative bacteria,while Escherichia coli is the most common pathogen,the detection rate of MRSA is lower than other surveillance data in the same period in China;carbapenem-resistant Klebsiella pneumoniae and Escherichia coli are at a low level as shown in this surveillance.

Objective: To evaluate the impact of psoriasis on spatial learning and memory abilities in mouse models by using Morris water maze. Methods: Twenty healthy male C57BL/6J mice aged 10 months were randomly and equally divided into 2 groups: psoriasis group topically treated with imiquimod 5% cream on the back once a day for a week, and control group topically treated with vaseline once a day for a week. After successful establishment of mouse models, the Morris water maze (MWM) test was used to assess the learning and memory abilities in the mice in the 2 groups. Results: In the place navigation experiment, the escape latency was significantly longer in the psoriasis group (38.24 ± 13.59 s) than in the control group (14.28 ± 3.80 s, t = 5.37, P < 0.01) . In the spatial probe test, the number of times passing through the platform (1.70 ± 0.95 vs. 5.00 ± 1.76, t = 5.21, P < 0.01) , the duration of stay in the target quadrant (t = 2.80, P < 0.05) and the swimming distance (t = 5.74, P < 0.01) were all significantly lower in the psoriasis group than in the control group. The psoriasis group showed significantly decreased swimming distance in the second quadrant (t = 2.49, P < 0.05) , but significantly longer duration of stay in the fourth quadrant compared with the control group (t = 2.46, P < 0.05) . There were no significant differences in swimming distance or duration of stay in other quadrants between the psoriasis group and control group (all P > 0.05) . Conclusion The spatial learning and memory abilities were impaired in the mouse model of psoriasis.