OBJECTIVETo investigate into the method of "multi activity index evaluation and combination optimized of mult-component" for Chinese herbal formulas.

METHODAccording to the scheme of uniform experimental design, efficacy experiment, multi index evaluation, least absolute shrinkage, selection operator (LASSO) modeling, evolutionary optimization algorithm, validation experiment, we optimized the combination of Jiangzhi granules based on the activity indexes of blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio of liver tissue to body.

RESULTAnalytic hierarchy process (AHP) combining with criteria importance through intercriteria correlation (CRITIC) for multi activity index evaluation was more reasonable and objective, it reflected the information of activity index's order and objective sample data. LASSO algorithm modeling could accurately reflect the relationship between different combination of Jiangzhi granule and the activity comprehensive indexes. The optimized combination of Jiangzhi granule showed better values of the activity comprehensive indexed than the original formula after the validation experiment.

CONCLUSIONAHP combining with CRITIC can be used for multi activity index evaluation and LASSO algorithm, it is suitable for combination optimized of Chinese herbal formulas.

Algorithms ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Models, Theoretical

Objective To compare the efficacy and safety of low-dose and standard-dose alteplase intravenous thrombolytic therapy in patients with acute ischemic stroke and to investigate whether low-dose alteplase is more suitable for patients with acute ischemic stroke in China.Methods Patients with acute ischemic stroke treated with alteplase intravenous thrombolysis from July 2016 to December 2018 in Anhui No.2 Provincial People's Hospital were enrolled retrospectively.According to the dose of alteplase,they were divided into low-dose group (0.6 mg/kg,the total dose not exceeding 60 mg) and standard dose group (0.9 mg/kg,the total dose not exceeding 90 mg).The efficacy endpoint was the clinical outcome at 90 d after onset evaluated by the modified Rankin Scale (mRS).The mRS score 0-2 was defined as self-care in life,and 0-1 was defined as good outcome.The safety endpoints were the incidence of symptomatic intracerebral hemorrhage (sICH) within 24-48 h after thrombolytic therapy and the mortality at 3 months.Results A total of 103 patients were enrolled,including 45 in the low-dose group and 58 in the standard dose group.There were no significant differences in demography,baseline clinical data,as well as self-care and good outcome rates at 90 d between the 2 groups.The incidence of sICH in the low-dose group (National Institute of Neurological Disorders and Stroke criteria:2.22％ vs.17.24％;x2 =4.521,P=0.033) and mortality at 90 d (6.67％ vs.24.14％;x2 =4.417,P =0.036) were significantly lower than those in the standard dose group.Conclusion The efficacy of low-dose alteplase in the treatment of acute ischemic stroke was comparable to that of standard dose,but the incidence of sICH and mortality at 90 d were significantly reduced,which might be more suitable for Chinese patients.

Objective To study the effect of remote limb isehemic postconditioning (RLIPC) on posterior circulation ischemia vertigo (PCIV). Methods Seventy patients with PCIV, admitted to our hospital from January 2013 and June 2014, were randomly divided into control group and therapy group (n=35). The patients of control group were treated with routine medicine, and those of therapy group were treated with RLIPC and routine medicine. Before and after treatment, dizziness assessment rating scale (DARS) and dizziness handicap inventory (DHI) scale were used to evaluate the changes of manifestations; peak systolic velocity (PSV) and end diastolic velocity (EDV) of vertebra artery (VA) were evaluated by colour doppler ultrasound. Results Before treatment, no significant differences on DARS and DHI scores were noted between the two groups (P>0.05); after treatment, , the DARS and DHI scores in the therapy group were 26.03±4.24 and 60.91±10.15, respectively, which were significantly decreased as compared with those in the control group (28.80±5.16 and 68.11±12.44, t=2.388 and 2.584, P=0.000); PSV and EDV of VA in the therapy group were 49.97±7.69 and 16.90±2.80, respectively, which were significantly increased as compared with those in the control group (47.31±7.47 and 15.12± 2.74, t=-2.505 and-2.631, P=0.015 and 0.011). Conclusions RLIPC could alleviate the symptoms of PCIV, which might be related to increased blood flow of VA. RLIPC is simple and safe, and can be used in the treatment of PCIV.

OBJECTIVE:To establish a method for the determination of dendrobine and its metabolites M-250 and M-280 in mice plasma for the first time. METHODS:Mice were given dendrobine 60 mg/kg by intragastric administration,1 h later plasma were collected and treated. Using pseudoephedrine hydrochloride as internal standard and dendrobine reference substance as control, the plasma concentrations of dendrobine and its metabolites M-250 and M-280 were determined by UPLC-MS combined with quantitative analysis of multi-components by single marker. The separation was performed on Hypersil Gold C18 column with 0.1％formic acid-acetonitrile(gradient elution)at the flow rate of 0.3 mL/min. The column temperature was set at 40℃,and sample size was 5 μL. Heatable electrospray ionization (HESI) source, scan/ESI + were applied and operated in positive ion mode with atomization temperature of 300℃,ion transmission tube temperature of 350℃,the sheath gas velocity of 35 arb,the auxiliary air velocity of 15 arb,the spray voltage of 3.5 kV,the collision voltage of 30,40,50 eV. The mass-to-charge ratio of detection range were 100-1500. RESULTS:The endogenous substances of mice plasma had no interference with the content determination of dendrobine and its metabolites M-250 and M-280. The linear range of dendrobine were 9.13-912.94 ng/mL(r=0.9996). The limit of quantitation was 3.04 ng/mL. RSDs of intra-day and inter-day were all less than 7.5％(n=5 or n=3). The accuracy were 96.8％-107.5％(n=5). Matrix effects were 97.1％-106.0％(RSD=1.8％-4.7％,n=5). RSDs of the content of sample at 15℃ for 24 h,at -70 ℃ after three times freeze-thaw,at -70 ℃ for 15 d were lower than 12.8％ (n=3). The content of dendrobine in plasma sample of mice was (41.3 ± 5.7) ng/mL (n=12). The contents of its metabolites M-250 and M-280 were (493.0 ± 73.1) and (41.4 ± 3.0) ng/mL (n=12) with Relative correction factor of 1.0. CONCLUSIONS: The method is sensitive and accurate,and can be used for content determination of dendrobine and its metabolites M-250 and M-280 in mice plasma.

OBJECTIVE：To investigate the effects of gypenosides （GPs）on gene expression of major urinary proteins （Mups） in liver tissue of hypercholesterolemia model mice. METHODS ：C57BL/6J mice were divided into control （ND）group，model （HFD）group and GPs therapy （GP）group according to body weight （BW），with 11 mice in each group. Except for ND group ， other groups were given high-lipid diet to induce hypercholesterolemia model. From the 17th week of feeding ，ND group and HFD group were given constant volume of 0.1％CMC-Na solution intragastrically ；GP group were given GPs suspension （250 mg/kg） intragastrically，once a day ，for consecutive 22 weeks. BW ，the levels of blood glucose （BG）and blood lipid （TC，LDL-C）were detected in each group. Total RNA of liver tissue was extracted ，and reverse transcription library was constructed and RNA-seq sequencing was performed. The differentially expressed genes were screened by PCA ，volcano map and scatter plot. RT-qPCR was used for verification for differentially expressed genes. The correlation between the expression of differentially expressed genes and the above pharmacodynamic indexes was analyzed by bivariate analysis. RESULTS ：Compared with ND group ，BW，the levels of BG，TC and LDL-C in HFD group were increased significantly （P＜0.05）. Compared with HFD group ，above indexes of GP group were decreased significantly except for BW （P＜0.05）. PCA showed that the data of ND group and HFD group distributed in different quadrants ，and the data distribution of GP group was between above two groups. mRNA of Mup4，Mup5，Mup11，Mup15 and Mup21 in liver tissue of mice were increased significantly after treated with high-fat diet （P＜0.05）. mRNA of Mup3，Mup4， Mup5，Mup8，Mup12 and Mup21 were decreased significantly after treated with GPs （P＜0.05）. In ND group vs. HFD group and HFD group vs. GP group ，mRNA of Mup4，Mup5 and Mup21 genes changed significantly and the trend was opposite. Results of RT-qPCR verification showed that compared with ND group ，relative mRNA expression of Mup4，Mup5 and Mup21 gene were increased significantly in HFD group （P＜0.05）. Correlation analysis revealed that mRNA expression of Mup5 was positively correlated with the levels of TC and BG （r＝0.727 1，0.670 6，P＜0.05），mRNA expression of Mup4 and Mup21 were positively correlated with the level of BG （r＝0.737 8，0.721 5，P＜0.05）. CONCLUSIONS ：GPs can regulate the expression of Mups genes in liver tissue of hypercholesterolemia model mice ， and reduce glucose and lipid level through regulating the mRNA over-expression of Mup4，Mup5 and Mup21.