Warfarin is a well-accepted drug used for preventing thromboembolic diseases. It is important to monitor the dosage of warfarin. Prothrombin time is one of the screening tests of extrinsic coagulation path,which is the first choice to monitor the oral use of warfarin. Standardized prothrombin time, namely international normalized ratio ( INR ) is used to adjust warfarin dosage in clinical practice. Many herbal medicines and foods may enhance the effect of warfarin therapy,and some of them may weaken this effect,which can result in severe clinical complications.

OBJECTIVE:To systematically review the efficacy and safety of Kanglaite injection combined with radiothreapy in the treatment of the non-small cell lung cancer (NSCLC),and provide evidence-based reference for clinical treatment. METH-ODS:Retrieved from PubMed,Cochrane Library,EMBase,VIP,CJFD,Wanfang database and CBM,randomized controlled tri-als(RCT)about the efficacy and safety of Kanglaite injection combined with radiothreapy in the treatment of NSCLC were collect-ed. Meta-analysis was performed by using Rev Man 5.3 software after data extraction and quality evaluation with modified Jadad scale. RESULTS:Totally 9 RCTs were included,involving 561 patients. Results of Meta-analysis showed,Kanglaite injection com-bined with radiothreapy can significantly improve the effective rate [OR=2.99,95%CI(2.07,4.31),P<0.001] and improvement rate of life quality [OR=3.74,95%CI(2.36,5.92),P<0.001],and reduce the incidence of radiation pneumonitis [OR=0.23,95%CI (0.12,0.47),P<0.001] and radiation esophagitis [OR=0.10,95%CI(0.05,0.21),P<0.001] of NSCLC patients,the differences were statistically significant. CONCLUSIONS:Both the efficacy and safety of Kanglaite injection combined with radiothreapy in the treatment of NSCLC are superior to radiothreapy alone.

Objective: To investigate the genes differently expressed in the livers of Kkay diabetic and normal mice, providing data to prevent human from diabetes and its chronic complications. Methods: cDNA microarray chips containing 8 192 cDNAs were used to investigate the gene expression pattern of the liver in Kkay mouse. Results: One hundred and fifty four genes were screened out, comprising 68 complete cDNAs and expressed sequence tags, among them 40 genes were up regulated and 114 genes were down regulated. Conclusion: The pathogenesis of type Ⅱ diabetes is complicated, including the disorder of the metabolism of carbohydrate, fat and protein, and many functional abnormalities of a number of vital proteins. [

OBJECTIVE:To systematically evaluate therapeutic efficacy of Xuefu zhuyu decoction in the adjuvant treatment of unstable angina pectoris (UAP),and to provide systematic evidence-based reference in clinic.METHODS:Retrieved from PubMed,EMBase,Cochrane library,CJFD,Wanfang database,VIP and CBM,randomized controlled trials (RCTs) about Xuefu zhuyu decoction+conventional treatment (trial group) vs.single conventional treatment (control group) in the treatment of UAP were collected.Meta-analysis was performed by using Rev Man 5.2 statistical software after data extraction and Cochrane systematic review manual 5.1.0.RESULTS:Totally 12 RCTs were included,involving 1 252 patients.The results of Meta-analysis showed that total response rate [OR=3.56,95％CI(2.49,5.10),P＜0.001],serum HDL[WMD=0.25,95％CI(0.05,0.45),P=0.01] and the rate of ECG improvement [OR=2.76,95％CI(1.97,3.87),P＜0.001] of trial group were significantly higher than those of control group,while serum TC [WMD=-1.14,95％CI(-1.46,-0.82),P＜0.001],TG [WMD=-0.53,95％CI(-0.84,-0.22),P＜0.001] and CRP [WMD =-0.91,95 ％ CI (-1.14,-0.69),P＜ 0.001] levels of trial group were significantly lower than those of control group,with statistical significance.CONCLUSIONS:Therapeutic efficacy of Xuefu zhuyu decoction in adjuvant treatment have good therapeutic efficacy and can significantly improve the blood lipid and inflammatory factors level.

Objective To investigate the expression and significance of autophagy related gene in rats with non-alcoholic fatty liver disease (NAFLD).Methods In vivo model of NAFLD was established in SD rats by high fat diet (model group,n =24),while the rats with normal food were set as control group (n =18).The rats of each group were sacrificed at the end of 4,8,12 weeks respectively.Body weight,liver wet weight,liver function,liver lipid metabolism and other indicators were measured.Hepatic histology was evaluated by hematoxylin-eosin (HE) staining and oil red O staining.The identification of autophagy were morphologically visualized by transmission electron microscopy (TEM).The expression of autophagy related gene ATG7,beclin1,microtubule-associated protein 1 lightchain3 (LC3) were detected by real-time quantitative RT-PCR (qRT-PCR) for mRNA levels.Result ① Compared with the control group at the corresponding time point,the weights of the mice and their livers.②Hepatic oil red O staining areas and density in high fat diet group all increased.HE staining revealed different degrees of macrosteatosis accompanied with intralobular inflammatary foci.With a remarkable histological change of NASH (typical hepatocellular ballooning and perisinusoidal fibrosis) about 80％ of mice from high fat diet group had NASH [NAFLD activity score (NAS) ≥5] at the end of 12 weeks.③ TEM pictures showed that autophagy bubble appeared since high fat diet feeding for 4 weeks.④ The relative expression of ATG7,Beclin1,LC3-Ⅰ,LC3-Ⅱ at mRNA level were up-regulated after high fat diet,and reached their peak at the end of 8 weeks when compared with the control group.The differences can be applied to statistical significance (P ＜ 0.05).The expression of these autophagy related genes in rats of high fat diet group were down-regulated at the end of 12 weeks,which had no difference the control group.Conclusion ①High fat diet feeding is able to induce a rat model of NAFLD.②The expression level of autophagy related genes is altered during high fat diet treatment.③Autophagy may take part in the occurrence and development of NAFLD.

Objective The aim of this study was to investigate how fish oil rich diet affected nonalcoholic steatohepatitis (NASH) induced by high fructose high fat high cholesterol diet in mouse.Methods 45 C3H mice aged 6 weeks were divided into 3 groups:normal diet group (control),lard rich diet group as model group (lard),fish oil rich diet (fish oil).Mice were sacrificed at the end of week 4,8,16,5 mice at each time point.Blood and liver were collected to test biochemical parameters,liver index,liver pathology and mRNA expression of inflammation associated gene.Results total cholesterol (TC) and serum ALT,AST increased significantly comparing to control (P ＜ 0.001),fish oil intervention inhibited these increases (P ＜0.05).The expression of monocyte chemotactic protein-1 (MCP-1) was upregulated,most dramatically at week 4,in lard group.While the mRNA level of MCP-1 is lower in fish oil group than lard group.TNF-α and TGF-β gene expression also rise at week 8,this trend diminished in fish oil group.HE staining showed apparent steatosis and inflammation infiltration at week 8 and 16 in lard group,while inflammation infiltration was weaker in fish oil group.The expression of kupffer cell marker gene CD68 elevated in lard group,fish oil diet down regulated this elevation.Conclusion Fish oil was able to protect liver from NASH related injury induced by high fructose high fat high cholesterol diet.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) for quantitative determination of liver fat and iron content through a rat model of non-alcoholic fatty liver disease (NAFLD) induced by methionine-choline deficient (MCD) diet.Methods:Sixty SD rats were randomly divided into experimental (MCD-diet group, n = 30) and normal control group (normal diet, n = 30). Rats were subjected to special MRI examinations at the ends of 2, 4, and 8 weeks. Proton density fat fraction (PDFF) and R2* value were obtained, and then the rats were sacrificed. The liver tissues were stained with HE, Prussian blue, etc. Liver tissue non-heme iron (NHI) homogenate was determined by flame atomic absorption spectrometry. According to different data, one-way analysis of variance, t-test or χ2 test was used for statistical analysis. Results:PDFF and R2 * values in the MCD diet group at 2, 4 and 8 weeks were 23.37% ± 9.20%, 28.07% ± 6.84%, 25.40% ± 7.04% ( P < 0.01) and 90.58 ± 15.92, 104.12 ± 13.47, 106.35 ± 15.76 ( P < 0.05), respectively, which were significantly higher than the normal control group PDFF (2.39% ± 0.50%, 2.45% ± 0.45%, 3.26% ± 0.80%) and R2* (48.93 ± 7.90, 54.71 ± 5.91, 64.25 ± 15.76). Additionally, with the disease progression, R2 * had gradually increased, which was consistent with the NHI trend in liver tissue homogenates of each group. Conclusion:MRI, as a non-invasive quantitative method, can accurately assess liver fat and iron content in fatty liver disease, and with the degree of severity of fat changes, iron deposits tend to increase.

Objective:To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease.Methods:Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction.Results:Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ??the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion:Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

OBJECTIVETo develop and evaluate a mouse model of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-fructose (HFHFr) diet.

METHODSSix-week-old C3H mice were randomly divided into groups for HFHFr diet experimental modeling, high fat-only (HF) diet controls, high fructose-only (HFr) diet controls, and standard chow (SC) diet controls. The standard HFHFr diet was modified so that it consisted of 76.5% standard chow, 12% lard, 1% cholesterol, 5% egg yolk powder, 5% whole milk powder, and 0.5% sodium cholate, along with 20% fructose drinking water. At the end of experimental weeks 4, 8, and 16, measurements were taken for the NASH-related parameters of body mass, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile, and wet liver weight (upon sacrifice). In addition, histological changes in the liver were evaluated by hematoxylin-eosin (HE) and oil red O staining. The significance of differences between groups was assessed by statistical analysis, using the

METHODSof t-test, Wilcoxon rank sum test, x2 test, F test or Fisher's test as appropriate.

RESULTSAs compared to the mice in the SC group at the corresponding time points, the mice in the HFHFr and HF groups showed significantly higher body mass and wet liver weight, as well as more extensive and robust lipid disposition in hepatic tissues as evidenced by oil red O staining. However, HE staining indicated that the HFHFr and HF groups had different degrees of macrosteatosis accompanied with intralobular inflammatory foci, with the former showing more remarkable NASH-related histological changes. Analysis at the end of week 16 showed that about 80% of the mice in the HFHFr group had developed NASH [nonalcoholic fatty liver disease (NAFLD) activity score (NAS): less than 5]. The levels of low-and high-density lipoprotein (LDL and HDL) cholesterol, as well as the levels of ALT and AST, were increased from the end of week 4 to the end of week 8 for the HFHFr and HF groups. At the end of week 16, the two groups differed in the extent of increase in total cholesterol and LDL and HDL cholesterol, with only the HFHFr group showing statistically significant changes. Specifically, at the end of week 16, the HFHFr group showed ALT levels of 108.5 +/- 93.34 U/L (F=5.099, P =0.005 vs. HF group: 44.30 +/- 35.71 U/L, HFr group: 46.70 +/- 17.95 U/L, SC group: 24.70 +/- 6.57 U/L), AST levels of 316.30 +/- 208.98 U/L (F=6.654, P=0.001 vs. HF: 132.12 +/- 75.43 U/L, HFr: 143.30 +/- 38.53 U/L, SC: 122.60 +/- 12.76 U/L), total cholesterol levels of 5.18 +/- 0.58 mmol/L (F=72: 470, P =0.000 vs. HF: 3.94 +/- 0.75 mmol/L, HFr: 2.30 +/- 0.50 mmol/L, SC: 2.02 +/- 0.24 mmol/L), HDL cholesterol levels of 3.05 +/- 0.49 mmol/L (F=25.413, P =0.000 vs. HF: 2.65 +/- 0.54 mmol/L HFr: 1.77 +/- 0.47 mmol/L, SC: 1.58 +/- 0.16 mmol/L), LDL cholesterol levels of 1.11 +/- 0.23 mmol/L (F =83.297, P =0.000 vs. HF: 0.72 +/- 0.17 mmol/L, HFr: 0.27 +/- 0.04 mmol/L, SC: 0.20 +/- 0.05 mmol/ L).

CONCLUSIONThe present study suggests that a mouse model of NASH can be successfully induced by a 16-week modified HFHFr diet.

To investigate the effect of glycyrrhizinate and phospholipids (DGPL) complex on inflammatory gene expression in cell inflammation model induced by palmitic acid (PA).Huh7 cells were divided into control, PA and PA+DGPL groups. For control group, cells were treated with BSA; for PA group, cells were incubated with 0.2 mmol/L saturated fatty acid PA, PA+DGPL group was given 20 μmol/L or 100 μmol/L DGPL in addition to 0.2 μmol/L PA. After 24 h, the expression of inflammation-related genes COX-2 and iNOS and endoplasmic reticulum (ER) stress-related gene GRP78 was determined by RT PCR. Oil red staining was conducted to observe the effect of DGLP on steatosis.Compared with control group, the expression of COX-2, iNOS and GRP78 in PA group was enhanced to 6.07±0.73(<0.05), 3.18±0.91 (<0.01) and 3.21±1.00(<0.05), respectively. Compared to control group, the expression of COX-2,iNOS and GRP78 in 100 μmol/L DGPL group was reduced to 2.40±0.76, 1.60±0.49 and 1.17 ±0.42 (<0.05); and 20 μmol DGPL had similar inhibition effect on COX-2 and iNOS elevation induced by PA (<0.01,<0.05 respectively). In addition, DGLP enhances the steatosis of Huh7 cells as demonstrated by oil red staining.PA can induce the up-regulated expression of inflammation associated genes COX-2, iNOS and ER stress-associated gene GRP78 in Huh7 cells. DGPL is able to protect Huh7 cells from PA induced inflammatory gene expression and the beneficial effect may be partially due to its unsaturated phospholipid component, which may improve ER stress and enhance steatosis.