OBJECTIVE To evaluate the quality of Zhachong-13 pills.METHODS The contents of agarotetrol， costunolide， hypaconitine， dehydrocostus lactone， mesaconitine， aconitine， liquiritigenin， glycyrrhizic acid， ellagic acid， liquiritin， corilagin， and gallic acid in 18 batches of samples were determined by high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method. Cluster analysis （CA） was performed using the Microbioinformatics online analysis platform. Principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed using SIMCA 14.1 software. Random forest， extremely randomized trees， and extreme gradient boosting machine learning models were constructed using the SPSSAU online analysis platform. The comprehensive quality of the samples was evaluated by the entropy weight-technique for order preference by similarity to ideal solution （TOPSIS） method.RESULTS The contents of the above 12 components were 104.331-694.382， 652.217-1 085.075， 6.051-130.980， 612.174-1 417.179， 1.018-32.239， 0.953-24.967， 65.552-652.239， 2 019.412-5 385.807， 52.867-4 990.450， 156.307-883.180， 10.142-475.722， and 1 102.863-4 826.396 μg/g， respectively. The results of CA and PCA showed that the 18 batches of samples were divided into two categories： S1-S6， S10-S15 were grouped into one category， while S7-S9 and S16-S18 were grouped into another category. The OPLS-DA results showed that the variable importance in projection values of mesaconitine， glycyrrhizic acid， liquiritin， ellagic acid， hypaconitine， liquiritigenin， agarotetrol， gallic acid， and dehydrocostus lactone were greater than 1. The results of the three machine learning models showed that ellagic acid and hypaconitine had relatively large differential contributions. The entropy weight-TOPSIS results showed that the overall quality of samples from manufacturer B was superior to that of the other four manufacturers.CONCLUSIONS The established method is stable and feasible， and can be used to evaluate the quality of Zhachong-13 pills， in combination with multivariate statistical analysis. Ellagic acid and hypaconitine are differential markers that affect its quality.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective To explore the effect and potential mechanism of total lignans of syringae ramuls(TLS)against liver cancer u-sing in vitro cellular assays,network pharmacological and molecular docking.Methods Flow cytometry was performed to detect the effect of TLS on apoptosis and cycle of HepG2 cells.TL components were collected by literature search;drug-like properties and synthetic scores of components were assessed by ADMETlab;toxicological parameters of components were predicted by ProTox-Ⅱ;TLS component targets were predicted by Swiss Target Prediction website;GeneCards,OMIM,DisGeNET,and PharmGKB databases were used to screen the related targets of liver cancer;The"component-disease-target"network diagram was constructed by Cytoscape software and the"protein-protein interaction"(PPI)network diagram was constructed by STRING platform;and DAVID database was used to analyse GO,KEGG and WIKI metabolic pathways.Results TLS at 50-200μg/ml could significantly inhibit the proliferation of HepG2 cells,induce apoptosis and block the cell cycle.The main components of TLS in anti-liver cancer were 31 active components,such as(-)matairesinol,(-)-secoisolariciresinol,and pinnatifolin A,which mainly acted on 82 key targets such as Akt1,Bel-2 and EGFR,which were mainly enriched in the cancer pathway,EGFR tyrosine kinase inhibitor resistance,cycle and apoptosis signaling pathways.Conclusion TLS may play an anti-liver cancer effect through multi-components,multi-targets,and multi-pathway.

Objective To explore the effect and potential mechanism of total lignans of syringae ramuls(TLS)against liver cancer u-sing in vitro cellular assays,network pharmacological and molecular docking.Methods Flow cytometry was performed to detect the effect of TLS on apoptosis and cycle of HepG2 cells.TL components were collected by literature search;drug-like properties and synthetic scores of components were assessed by ADMETlab;toxicological parameters of components were predicted by ProTox-Ⅱ;TLS component targets were predicted by Swiss Target Prediction website;GeneCards,OMIM,DisGeNET,and PharmGKB databases were used to screen the related targets of liver cancer;The"component-disease-target"network diagram was constructed by Cytoscape software and the"protein-protein interaction"(PPI)network diagram was constructed by STRING platform;and DAVID database was used to analyse GO,KEGG and WIKI metabolic pathways.Results TLS at 50-200μg/ml could significantly inhibit the proliferation of HepG2 cells,induce apoptosis and block the cell cycle.The main components of TLS in anti-liver cancer were 31 active components,such as(-)matairesinol,(-)-secoisolariciresinol,and pinnatifolin A,which mainly acted on 82 key targets such as Akt1,Bel-2 and EGFR,which were mainly enriched in the cancer pathway,EGFR tyrosine kinase inhibitor resistance,cycle and apoptosis signaling pathways.Conclusion TLS may play an anti-liver cancer effect through multi-components,multi-targets,and multi-pathway.

OBJECTIVE：To optim ize ethanol extraction technology of Mongolian medicine Naru- 3. METHODS ：The L 9（34） orthogonal design was used to optimize ethanol extraction technology of Mongolian medicine Naru- 3 with solid-liquid ratio ，ethanol volume fraction and extraction time as factors ，using comprehensive scores for the contents of benzoylaconitine ，benzoylneoaconitine， benzoylhypoaconitine，aconitine，neoaconitine，hypoaconitine，piperine and gallic acid as indexes. RESULTS ：The optimal ethanol extraction technology was that solid-liquid ratio of 1∶10（g/mL），ethanol volume fraction of 75％，extracting for 1.5 h. After 3 times of validation tests ，average contents of above 8 components in ethanol extract from Naru- 3 were 1.69，1.48，14.69，0.28， 0.05，0.08，26.01，17.33 mg/g（RSDs were 0-4.96％，n＝3），respectively. Average comprehensive score was 19.03（RSD＝1.42％， n＝3）. CONCLUSIONS ：The optimal ethanol extraction technology of Mongolian medicine Naru- 3 is stable and feasible.

OBJECTIVE： To screen the hepatoprotective active fractions from Ixeris chinensis and study its chemical constituents. METHODS：The petroleum ether，ethyl acetate，n-butanol and residual water fractions from 70％ ethanol extract of I.chinensis were extracted by systematic solvent method. Human hepatocytes HL-7702 were induced by acetaminophen to induce liver injury model. MTT method was used to detect the protective effect of the above fractions（40 μg/mL，by the dosage of crude drug）on injured cells，and the active fractions were screened. The active fractions were separated and purified by silica gel column and Sephadex column chromatography. The structure of the compounds were identified by physical and chemical properties and spectral data （hydrogen spectrum，carbon spectrum）. RESULTS：After treated with different fractions of I. chinensis，the cell survival rate of each administration group was increased significantly，compared with model group（P＜0.01），and the n-butanol and water fractions had the strongest activity （the cell survival rates were 49.3％ and 52.2％ ，respectively）. Six compoundswere isolated from n-butanol fraction and identified as sonchifolignan A（Ⅰ），apigenin-7-O-β-D-glucopyranoside methyl ester（Ⅱ），luteolin-7-O-β-D-glucuronopyranoside methyl ester （Ⅲ），luteolin-7-O-β-D-glucopyranoside （Ⅳ），apigenin-7-O-β-Dglucopyranoside（Ⅴ）and luteolin（Ⅵ）. CONCLUSIONS：The n-butanol fraction is regarded as an effective position for protecting liver，and flavonoids are the main active omponents.KEYWORDS Ixeris chinensis；Hepatoprotective activi

Objective To investigate the target organs function damage in elderly patients with H type hypertension and its association with blood pressure variability.Methods Ninety-two patients with H type hypertension in the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to January 2016 were collected as the observation group and contemporaneous 135 elderly patients with non-H type hypertension were collected as the control group.The main observation indicators included 24 h systolic/diastolic blood pressure variability,24 h average systolic/diastolic blood pressure,glomerular filtration rate(GFR),serum creatinine,24 h urinary microalbumin,carotid intima-media thickness and left ventricular mass index.Results Compared with the control group,24 h systolic blood pressure variability,24 h diastolic blood pressure variability,creatinine,24 h urinary microalbumin,carotid intima-media thickness and left ventricular mass index in the observation group were significantly increased(P＜0.05);GFR was significantly decreased (P＜0.05).The multiple linear regression analysis showed that 24 h systolic blood pressure variability was the factors affecting GFR (P＜0.05);24 h systolic blood pressure variability was the factor affecting~the creatinine level (P＜0.05);24 h systolic blood pressure,24 h systolic blood pressure variability and 24 h diastolic blood pressure variability were the influence factors of carotid intima-media thickness (P＜0.05);24 h systolic blood pressure variability was the influence factor of left ventricular mass index (P＜0.05).Conclusion The target organs function damage in the patients with H type hypertension is serious,and the blood pressurevariability enlargement is the influencing factor of target organs function damage.

Objective To investigate the protective effect of GuanXinShiWeiWan on ischemia reperfusion(I-R) injury rat.Methods 50 Wistar rats were randomly divided into normal group, model group, GuanXinShiWeiWan low ( 0.3 mg/kg ) and high ( 0.9 mg/kg ) dose group and positive group, each had 10 rats.Adopting the model of ischemia reperfusion injury of isolated rat hearts, the contents of SOD,MDA,LDH,CK and Ca2 +-ATP, Ca2 +-Mg2 +-ATP, Na +-K +-ATP in cardiac muscle tissue were tested and compared.Results Compared with model group, GuanXinShiWeiWan significantly improved the activities of SOD、Ca2 +-ATP,Ca2 +-Mg2 +-ATP and Na +-K +-ATP (P<0.05 or P<0.01) in cardiac muscle tissue which injured by ischemia reperfusion, while reducing markedly the contents of MDA,LDH,CK(P<0.05 or P<0.01).Conclusion GuanXinShiWeiWan can profect the cardiac muscle of ischemia reperfusion.