Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism.@*METHODS@#The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05).@*CONCLUSIONS@#YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.

Protective effect and mechanism of ginsenoside Rg1 on H2O2induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro / 中国药理学与毒理学杂志

OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1 (Rg1) on H2O2-induced hippocampal neurons aging in vitro. METHODS The primary culture hippo-campal neurons(7 d)were randomly placed into six groups:normal control group,H2O2(200 μM)treat-ment group,and H2O2+Rg1(1,5 and 10μM)groups.The neurons were with Rg1(1,5 and 10 μmol·L-1) for 6h. H2O2(200 μmol·L-1) was added to the medium and incubate for 18 h. The Dihydroethidium (DHE) staining was performed for ROS production assessment. The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis. The immunoblot was used to deter-mine the expression of β-Gal,NOX2,p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L-1)significantly reduced the ROS production, attenuated H2O2-induced neuronal damage and apoptosis (P<0.05, P<0.01). The immunoblot results showed that Rg1(5 and 10 μmol·L-1)treatment significantly decreased the expression of β-Gal,NOX2, p22phox,p47phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally, Rg1(5 and 10 μmol·L-1)treatment significantly decreased IL-1β and IL-18 release in the supernatant. CONCLUSION The protective effect of Rg1 in H2O2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.

Sensitivity and specificity of modified Los Angeles prehospital stroke green / 中华神经医学杂志

Objective To evaluate the sensitivity and specificity of modified Los Angeles prehospital stroke screen (MLAPSS) in the diagnosis of acute stroke. Methods Prehospital personnel and physicians in the Emergency Department of 3 hospitals were trained for appropriate use of MLAPSS. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, and Youden's index of MLAPSS for diagnosis of acute stroke were evaluated in patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage. Results Of a total of 2016 patients, 531 met the screening criteria of MLAPSS, among whom 157 had a final diagnosis of acute symptomatic cerebrovascular disease, including 82 with ischemic stroke, 17 with transient ischemic attack and 58 with intracerebral hemorrhages. The sensitivity, specificity and Youden index of MLAPSS for acute stroke diagnosis were 89% (95%CI: 85, 95), 95% (95%CI: 93, 97) and 0.85 (95%CI: 0.76, 0.94), with positive and negative predicted values of 89% (95%CI: 82, 95) and 96% (95%CI: 90, 100), and positive and negative likelihood ratios of 18 and 0.11, respectively. In the 531 patients, the missed diagnosis rate was 10% and the misdiagnosis rate was 5%. The average time to complete MLAPSS screening was 4 mitt 17 s. Conclusions MLAPSS has a relatively high sensitivity in the diagnosis of acute stroke with reduced misdiagnosis rate and high levels of specificity and predictive value. With easy operation, MLAPSS allows efficient screening of patients with acute stroke.

Human parvovirus B19 infection in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To investigate the relationship between parvovirus B19 infection and systemic lupus erythematosus(SLE).Methods Sera from 51 patients with SLE and 20 normal controls were exam- ined for IgG and IgM antibodies against parvovirus BI9 by ELISA(produced by IBL Hamburg Company, Germany).Results Anti-Bl9 antibodies were found more frequently in sera from SLE patients than in normal controls,IgM and [gG antibodies were detected in 11(17.65%)and 9(21.57%)of 51 SLE pa- tients respectively.It was observed that the SLEDAI scores were higher in patients with B19 IgM positive group than those of the negative group(P＜0.05).The sera levels of ALT/AST were elevated more frequently in patients with BI9 IgM positive group than in negative group(P＜0.05).However,there was no association between the presence of anti-IgM and clinical manifestations in patients with SLE(P＞0.05).Five SLE pa- tients with positive B19 IgM were followed up for 2 years.SLEDA1 scores of these patients were markedly decreased(P＜0.05),but the levels of auto-antibodis(ANA,dsDNA)didn't change(P＞0.05).And the levels of ALT/AST decreased as usual.Conclusions It is suggested that parvovirus B19 infection may ex- acerbate the onset of SLE,but we eould not find a correlation between parvovirus B19 infection and prog- nosis of the disease.

A randomized controlled study of Shenfu injection combined vinorelbine chemotherapy on the quality of life of elderly non-small cell lung cancer patients / 中国癌症杂志

Background and purpose:Although the third-generation chemotherapeutic agents combined with platinum have shown good effect on non-small-cell lung cancer(NSCLC),whether the regimen is the best for elderly patients with NSCLC still is controversial.The aim of his study was to investigate the efficacy of Shenfu injection combined with Vinorelbine on the improvement of quality of life(QOL)in elderly NSCLC patients.Methods:A randomized single blind trial method was used.46 patients with stageⅢb-Ⅳof NSCLC were randomly divided into research group and control group.In the research group,the patients were treated with 50 ml of Shenfu injection from day 1 to 14,combined with Vinorelbine(NVB)25 mg/m~2 on day 1 and 8.In the control group,the patients were only treated with NVB 25 mg/m~2 on day 1 and 8.After two cycle's of treatment,QOL,efficacy and toxicity were observed. Results:The QOL was enhanced in both research group and control;however,the difference of KPS after treatment in the research group was markedly higher than in the control(14?10 vs.8?10,t=2.116,P=0.04),improvement rate of QOL was better than in the control(76.2% vs.45.0 %,x~2=4.188,P=0.041),treatment related toxicity in the research group was also markedly lower than that in the control(x~2=3.866,P=0.049),but the difference of efficacy between the two groups was not significant(14.3% vs.15.0%,x~2=0.161,P=0.688).Conclusions:ShenFu injection combined with Vinorelbine could enhance QOL in elderly NSCLC patients.

Construction of NF-?B/p65-targeting RNAi combinant adenovirus vector and its suppressive effect on the expression of p65 in ECV304 cells / 中华内分泌代谢杂志

Objective To construct RNAi combinant adenoviral expressive vectors specific to p65 subunit of NF-?B and to observe their gene silencing effect on p65 subunit.Methods Three pairs of complementary. single-strand DNA oligos targeting three various sites of p65 mRNA were designed and synthesized.Annealling was used to generate double-strand oligos(ds-oligos),and then the ds-oligos were cloned into pENTR~TM/u6 to generate the entry clone named pENTR.Recombination reaction in vitro with the pENTR and pAd/BLOCK-iT~TM- DEST was used to creat the adenovirus plasmid which contains the RNAi cassette.Then,the adenovirus plasmids digested with PacI were transfected into HEK293A cells to product adenovirus,and latter infected the HEK293A cells to amplify the adenoviral stock.Plaque forming assay was used to titer the adenoviral stock.The p65 gene silencing effect induced by the RNAi adenovirus was detected by Western blot and immunocytochemistry assay in ECV304 cells.Results The RNAi adenovirus specific to p65 subunit of NF-?B were produced with titer of 3.0 x 10~9pfu/ml to 2.5?10~10pfu/ml.The expression of p65 protein in ECV304 cells could be down-regulated efficiently by the RNAi adenovirus 48-72 h after infection,which would last for more than 6 days after infection.Conclusion RNAi adenovirus is an important tool inhibiting the expression of target gene efficiently.