Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer's disease and vascular dementia / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.

Monoterpenoids from Paeoniae Radix Rubra based on UPLC-Q-TOF-MS / 中国中药杂志

The ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to conduct the qualitative analysis of the monoterpene chemical components from Paeoniae Radix Rubra. Gradient elution was performed on C_(18) HD(2.1 mm×100 mm, 2.5 μm) column with a mobile phase of 0.1% formic acid(A) and acetonitrile(B). The flow rate was 0.4 mL·min~(-1) and the column temperature was 30 ℃. MS analysis was conducted in both positive and negative ionization modes using electrospray ionization(ESI) source. Qualitative Analysis 10.0 was used for data processing. The identification of chemical components was realized by the combination of standard compounds, fragmentation patterns, and mass spectra data reported in the literature. Forty-one monoterpenoids in Paeoniae Radix Rubra extract were identified. Among them, 8 compounds were reported in Paeoniae Radix Rubra for the first time and 1 was presumed to be the new compound 5″-O-methyl-galloylpaeoniflorin or its positional isomer. The method in this study realizes the rapid identification of monoterpenoids from Paeoniae Radix Rubra and provides a material and scientific basis for quality control and further study on the pharmaceutical effect of Paeoniae Radix Rubra.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS / 中国天然药物

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Effects of Si-Wu Decoction and its active components on cytochrome P450 in rats / 中国药理学通报

Aim To study the influence of Si-Wu De-coction (SWD ) and its active components on cyto-chrome P450 activity and mRNA expression in rats in order to provide an experimental basis for compatibility of SWD.Methods SWD and its active components were intragastrically administrated for seven days,the doses of SWD was 10 g · kg -1 · d -1 ,the doses of fructose,ferulic acid,ligustrazine,peoniflorin were 0.334,0.002,0.011 and 0.022 g·kg -1 ·d -1 ,re-spectively.After administration for seven days,rats were executed,and liver microsomes were prepared. The effects of SWD and its active components on cyto-chrome P450 in rats were investigated by hybrid probe and liver microsomes incubation method.The level of mRNA expression in liver was detected by real-time quantitative polymerase chain reaction using specific target primers for CYP450 genes.The level of protein expression of CYP2B1 was detected by Western blot. Results Compared with the control group,fructose significantly decreased the activity of CYP1A2, CYP2B6,CYP2C9,CYP2D6;ferulic acid significantly decreased the activity of CYP2C9,CYP2B6;ligus-trazine significantly decreased the activity of CYP1A2, CYP2C9,CYP2B6;peoniflorin significantly decreased the activity of CYP2D6,CYP2B6;fructose,ferulic acid,peoniflorin inhibited the mRNA expression of CYP2B1;fructose,ferulic acid,ligustrazine and peon-iflorin also inhibit the protein expression of CYP2B1. Conclusion Fructose,ferulic acid,peoniflorin inhib-it the activity of CYP2B1,decrease the expression lev-els of mRNA and protein of CYP2B1.

Nutritional intervention on T2 DMs in Community of Yangpu District in Shanghai (2014) / 上海预防医学

Objective To investigate the effect of nutritional intervention on elderly patients with type 2 diabetes mellitus (T2DM) in community, so as to control T2DMs more effectively and improve the patients'life quality and prolong their life span. Methods The intervention group (130 cases) with a definite diagnosis of T2DM were included from one neighborhood of two communities respectively.So were the control group (130) by the same approach.The two groups were matched in sex and age.In addition to medical treatment, the intervention group was given diet guide, nutritional education, nutritional intervention and so on and the control group was given drug treatment alone.The data obtained was analyzed by group t test. Results The cases in the two groups had the same diet habit before intervention.After intervention, as compared with the control group, the intervention group had the diet constitution improved; and it was found that the blood sugar 2 hours after meal, total cholesterol, low density lipoprotein cholesterol,fasting plasma glucose, total triglyceride and HbAlc were significantly lower, high-density lipoprotein cholesterol was significantly higher ( P <0 .05 ) . Conclusion The nutritional intervention can improve the glucose metabolism and reduce the risk factors in the T2DM population.

Study of Tobacco Sensory Evaluation Model in Near Infrared Spectroscopy by Semi Supervised-Partial Least Squares / 分析化学

Semisupervisedmakesfulluseoflargeamountsofunlabeledsamplestomakeuptheinsufficiency of labeled samples. Since it is difficult to obtain a large number of accurate labeled samples and it is a good way for modeling by using a small amount of labeled samples or a large number of inaccurate samples, we proposed a new method named as semi-supervised partial least squares ( SS-PLS) to optimize model based on semi supervised learning. We used 211 samples of tobacco near infrared spectrum and sensory evaluation for modeling and used SS-PLS method to optimize tobacco sensory evaluation model. In the optimized model, the coefficient of determination ( R2 ) can reach up to 90%, the ratio of performance to deviation ( RPD) can reach up to 3 . 0 , and the standard error of cross validation and the standard error of prediction ( SECV and SEP) are below 1. 0. We divided the original sensory evaluation and SS-PLS optimized data into three grades of excellent, medium and poor in accordance with the fixed threshold, the result using projection model of based on principal component and Fisher criterion ( PPF ) shows that the classification of SS-PLS optimized data is better than the original sensory evaluation data. The SS-PLS method can solve the data representation problem of using small sample set for modeling and provides a new chemometrics method for near infrared spectroscopy modeling in case of obtaining a large number of accurately labeled samples is difficult.

Association of chronic obstructive pulmonary disease with coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) remains largely unknown. This study aimed to explore the association of COPD with CAD, especially with multi-vessel disease (VD).</p><p><b>METHODS</b>The data of 354 patients who underwent multi-detector computed tomography (MDCT) for suspected CAD were analyzed. Luminal narrowing was defined as at least one lesion 50% or greater stenosis. The analysis of serum biochemistry profile and spirometry were performed on all eligible patients, and the diagnosis of COPD was defined as the criteria of Global Initiative for Chronic Obstructive Lung Disease.</p><p><b>RESULTS</b>Patients with CAD had a significantly higher complication of COPD than those without CAD (11.8% vs. 3.7%, P < 0.001). Comparing with patients without COPD, those with COPD were more likely to have multi-VD, proportion of smoking and high C-reactive protein (CRP) (P < 0.001). Multivariate Logistic regression analysis revealed that the multi-VD was significantly correlated with COPD (P=0.012) and CRP (P=0.015).</p><p><b>CONCLUSIONS</b>There was a high complication of COPD in patients with CAD, and COPD may be a critical risk factor for CAD, especially for multi-VD. CAD and COPD were closely associated and the interplay of systemic inflammation might in part explain the relationship between them.</p>

Effect of Siwu decoction and its combined administration on hepatic P450 enzymatic activity and mRNA expression in rats / 中国中药杂志

To study the effect of Siwu decoction (SWD) compound and its combined administration on hepatic P450 enzymatic activity and mRNA expression in rats. Rats were orally administered with SWD and water decoction combined with other medicines for two weeks, and then sacrificed. Their livers were perfused with normal saline to prepare liver micrisomes. Mixed probe and liver microsome in vitro incubation method were adopted to detect the effect of SWD on hepatic cytochrome P450. The real-time quantitative polymerase chain reaction (Q-PCR) was used to detect the effect of SWD on the expression of hepatic cytochrome P450. Compared with the control group, the SWD compound group showed higher CYP1A2 enzymatic activity (P < 0.05); Rehmanniae-paeoniae, angelicae-paeoniae, angelicae-rhizome, paeoniae-rhizome groups had lower CYP1A2 and CYP2C19 enzymatic activities (P < 0.05); And the compound group, the single component group and the combination group showed lower CYP2B6 enzymatic activities (P < 0.05). The compound could up-regulated the mRNA expression of CYP2B1 (P < 0.05); And the four single components could down-regulated the mRNA expression of CYP2B1 (P < 0.05). SWD compound had the effect in inducing CYP1A2 enzymatic activity. The rehmanniae-paeoniae group and the angelicae-paeoniae group had identical enzymatic activity with the control group, but significant down-regulation in CYP1A2 enzymatic activity after being combined with paeoniae. The compound and its combined administration showed the inhibitory effect on CYP2B6 enzymatic activity, particularly being combined with angelicae. The compound showed identical effect with the four single components in terms of CYP1A2 mRNA expression and enzymatic activity.

Relationship between 6-minute walk test and pulmonary function test in stable chronic obstructive pulmonary disease with different severities / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between the 6-minute walk test (6MWT) and pulmonary function test in stable chronic obstructive pulmonary disease (COPD) remains unclear. We evaluate the correlation of 6MWT and spirometric parameters in stable COPD with different severities. 6MWT data assessed included three variables: the 6-minute walk distance (6MWD), 6-minute walk work (6MWORK), and pulse oxygen desaturation rate (SPO(2)%).</p><p><b>METHODS</b>6MWT and pulmonary function test were assessed for 150 stable COPD patients with different severities. Means and standard deviations were calculated for the variables of interest. Analysis of variance was performed to compare means. Correlation coefficients were calculated for 6MWT data with the spirometric parameters and dyspnea Borg scale. Multiple stepwise regression analysis was used to screen pulmonary function-related predictors of 6MWT data.</p><p><b>RESULTS</b>The three variables of 6MWT all varied as the severities of the disease. The 6MWD and 6MWORK both correlated with some spirometric parameters (positive or negative correlation; the absolute value of r ranging from 0.34 to 0.67; P < 0.05) in severe and very severe patients, and the SPO2% correlated with the dyspnea Borg scale in four severities (r = -0.33, -0.34, -0.39, -0.53 respectively; P < 0.05). The 6MWD was correlated with the 6MWORK in four severities (r = 0.56, 0.57, 0.72, 0.81 respectively, P < 0.05), and neither of them correlated with the SPO(2)%. The percent of predicted forced expiratory volume in 1 second (FEV(1)% predicted) and residual volume to total lung capacity ratio (RV/TLC) were predictors of the 6MWD, and the maximum voluntary ventilation (MVV) was the predictor of the 6MWORK.</p><p><b>CONCLUSIONS</b>6MWT correlated with the spirometric parameters in severe and very severe COPD patients. 6MWT may be used to monitor changes of pulmonary function in these patients.</p>

Long-term non-invasive positive pressure ventilation in severe stable chronic obstructive pulmonary disease: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The evidence for non-invasive positive pressure ventilation (NIPPV) used in patients with severe stable chronic obstructive pulmonary disease (COPD) is insufficient. The aim of the meta-analysis was to assess the treatment effects of long-term NIPPV on gas change, lung function, health-related quality of life (HRQL), survival and mortality in severe stable COPD patients.</p><p><b>METHODS</b>Randomized controlled trials (RCTs) and crossover studies comparing the treatment effects of NIPPV with conventional therapy were identified from electronic databases and reference lists from January 1995 to August 2010. Two reviewers independently assessed study quality. Data were combined using Review Manager 5.0. Both pooled effects and 95% confidence intervals were calculated.</p><p><b>RESULTS</b>Five RCTs and one randomized crossover study with a total of 383 severe stable COPD patients were included. NIPPV improved gas change significantly when using a higher inspiratory positive airway pressures. The weighted mean difference (WMD) for the partial pressure of carbon dioxide in artery (PaCO2) was -3.52 (-5.26, -1.77) mmHg and for the partial pressure of oxygen in artery (PaO2) 2.84 (0.23, 5.44) mmHg. There were significant improvements in dyspnea and sleep quality, but gained no benefits on lung function. The standardized mean difference (SMD) for the forced expiratory volume in 1 second (FEV(1)) was 0.00 (0.29, 0.29). And the benefits for exercise tolerance, mood, survival and mortality remained unclear.</p><p><b>CONCLUSIONS</b>Patients with severe stable COPD can gain some substantial treatment benefits when using NIPPV, especially improvements in gas change, dyspnea and sleep quality. Studies of high methodological quality with large population, especially those based on a higher inspiratory positive airway pressures are required to provide more evidences.</p>

Safety and immunogenicity on three lots of influenza split vaccines among adults / 中华流行病学杂志

Objective To evaluate the irnmunogenicity, safety and stability of the manufacture process regarding three consecutive lots of influenza split vaccines (Anflu ). Methods A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers. A total of 566 subjects aged 18 to 60 years were recruited and stratified into four age groups before randomly assigned into four groups. Each group would receive one dose of influenza vaccine from either one of the three lots ofAnflu or one lot of the licensed control vaccine. Each dose of the vaccines contained 15 μg of each of the H1N1, H3N2 and B type antigen. Safety was assessed through 30-minute observation for immediate allergic reaction and three-day observation after vaccination. HI antibody titers were determined before vaccination and on day 21, after vaccination. Results Mild adverse reaction was reported and the overall incidence rates on fever of the four groups were from 1.4% to 2.8% but no significant difference was observed between groups. Seroconversion rates of the three viral strains in four groups were 80.3% and above with fold increase as≥11.1 and protection rate was≥93.4%. For the three lots of investigated vaccines, all of the indexes of the three viral strains in four groups exceeded the standards on EMEA and FDA for influenza vaccine. Conclusion The three consecutive lots of Anflu appeared to be good, with both consistent immunogenieity and safety, indicating the stability of manufacture process.

Mutagen sensitivity in peripheral blood lymphocytes among coke-oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers.</p><p><b>METHODS</b>Ninty-four coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 64 non-coke-oven workers (control) were recruited into this study. PBL was challenged by 8 microg/ml BLM, a known carcinogen, to induce certain amount of DNA damage, the difference of olive tail moment (TM) measured by comet assay before and after BLM treatment reflected the sensitivity towards mutagens.</p><p><b>RESULTS</b>The distribution of age, sex, and prevalence of smoking and drinking were not significantly different between these two groups. The geometric mean of urinary 1-hydroxypyrene (1-OHP) was significantly higher in coke-oven workers than in controls (9.0 versus 1.5 microg/L, t = -9.317, P < 0.01). The coke-oven workers showed significantly higher sensitivity to BLM than controls (17.7 versus 14.9, t = -2.583, P = 0.01). A large inter-group difference in sensitivity to BLM was observed in both controls and coke-oven workers. Stratification analysis revealed the significant association between high 1-OHP level (> 9.0 microg/L) and increased sensitivity to BLM (F = 4.001, P = 0.05) among coke-oven workers. Smoking subjects showed a significant higher value of sensitivity than nonsmokers in controls but not in coke-oven workers. No significant difference was observed between age, drinking status, coking history or external exposure class and BLM sensitivity.</p><p><b>CONCLUSION</b>Exposure to coke oven emission could increase the sensitivity to mutagens, which might be a reason of high incidence of lung cancer among coke-oven workers.</p>

High performance liquid chromatography-mass spectrometry analysis of radix Angelica sciensis / 药学学报

<p><b>AIM</b>To analyze the chemical components in Danggui (the roots of Angelica sinensis (Oliv.) Diel).</p><p><b>METHODS</b>HPLC-MS/MS was used to identify the main components in Danggui. Furthermore, the MS fragmentation regularity of the phthalides was proposed. The mobile phase of HPLC consisted of 0.5% acetic acid in water and 0.5% acetic acid in acetonitrile, analytical column was Hypersil ODS2 (250 mm x 4.6 mm, 5 microm), flow rate 1.0 mL x min(-1), injected volume 2 microL. The ionization source was ESI in positive ion mode.</p><p><b>RESULTS</b>Ferulic acid, nine known phthalides and one unknown phthalide derivative were tentatively identified in chromatograms based on their MS data and the comparison of their UV spectra with those published in the literatures.</p><p><b>CONCLUSION</b>The structural information of phthalides was obtained via HPLC-MS/MS, which provides an accurate and fast method to identify the phthalides and provides more scientific information for quality control of Danggui.</p>

HPLC determination of caffeic acid in herba Lycopi / 中国中药杂志

<p><b>OBJECTIVE</b>To provide experimental data for the quality control of processed Paeonia lactiflora, a Chinese herbal medicine.</p><p><b>METHOD</b>Traditional processing of P. lactiflora was simulated, content of paeoniflorin and water extracts among different preparations were assayed by HPLC; The quantitative correlations among different processing conditions were analyzed, the effects of processing parameters on the contents of paeoniflorin and water extracts were assayed and analysed.</p><p><b>RESULT AND CONCLUSION</b>The controlled processing parameters were correlated with covariables which showed that processing procedures was controllable, and the heating temperature was a factor impacting the content of paeoniflorin.</p>

Study on GC fingerprint of the constituents in Herba Asari / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a method for GC fingerprint determination of the chemical constituents in Herba Asari.</p><p><b>METHOD</b>GC and GC-MS were used to optimize the fingerprint determination method, and identify the main peaks in the GC fingerprint.</p><p><b>RESULT</b>A preferable method for GC fingerprint determination of the chemical constituents in Herba Asari was established.</p><p><b>CONCLUSION</b>A general acquaintance of the chemical constituents in Herba Asari can be obtained by using the preferable GC fingerprint determination method, which is useful for quality evaluation of the crude drug of Herba Asari.</p>

Pharmacokinetic study on spinosin in rat plasma after oral administration of suanzaoren extract at a single dose / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of spinosin in rat plasma after oral administration of Suanzaoren extract using sulfamethoxazole (SMZ) as internal standard by RP-HPLC method.</p><p><b>METHODS</b>Plasma samples were deproteined with acetonitrile, followed by evaporation of the acetonitrile to dryness. The residual was then resolved in mobile phase and HPLC separation was achieved on a Hypersil C18 (5 microns, 200 mm x 4.6 mm ID) column at 35 degrees C. The mobile phase consisted of acetonitrile-water-acetic acid (15:85:1) at a flow rate of 0.7 mL.min-1. The UV detection wavelength was set at 334 nm.</p><p><b>RESULTS</b>The calibration curve was shown to be linear over the range from 18.1 to 903.5 micrograms.L-1 (r2 > or = 0.995). Mean recovery was 94.5%. Within-day and between-day precisions RSD were less than 9.0%. The limit of quantitation was 18.1 micrograms.L-1. The plasma spinosin was stable at -20 degrees C.</p><p><b>CONCLUSION</b>The simple, sensitive and accurate HPLC method developed has been applied to determine the pharmacokinetics of spinosin in rat plasma after having taken Suanzaoren extract at a single dose.</p>

Vectorial angle method for evaluating the similarity between two chromatographic fingerprints of Chinese herb / 药学学报

<p><b>AIM</b>To evaluate the similarity between two chromatographic fingerprints automatically with computer.</p><p><b>METHODS</b>Chromatogram can be treated as vector of hyperspace, and the similarity between them can be counted according to vectorial angle formula. This process was performed with software written in Visual Basic 6.0. The two main functions of this software are automatic peak tracking in two fingerprints under the same analytic condition and computing the similarity automatically.</p><p><b>RESULTS</b>The HPLC fingerprints of eleven kinds of Evodia rutaecarpa (Juss.) Benth (a traditional Chinese herb) from different sources were obtained and the similarities were calculated with this software. This method was shown to be a good way to evaluate the similarity between two fingerprints. A sample washed seven times with hot water can be clearly discriminated from other samples of Evodia rutaecarpa (Juss.) Benth with similar results.</p><p><b>CONCLUSION</b>This method is a good way to evaluate the similarity between two fingerprints and is helpful in quality control of traditional Chinese medicine.</p>