Influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Content Determination and Difference Analysis of 3 Saponins in Different Parts of Ypsilandra thibetica from Different Producing Areas / 中国药房

OBJECTIVE：To establish the method for content dete rmination of polyphyllin Ⅱ，Ⅵ，Ⅶ in Ypsilandra thibetica ， and to compare the differences of 3 saponins in different parts of Y. thibetica from different producing areas. METHODS ：HPLC method was adopted to determine the contents of polyphyllin Ⅱ，Ⅵ，Ⅶ in whole grass part and underground part of Y. thibetica from 10 producing areas. The determination was performed on Kromasil C 18column with mobile phase consisted of acetonirile-water （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was 35 ℃，and detection wavelength was set at 203 nm；sample size was 10 μL. With the contents of 3 saponins as the index ，20 batches of Y. thibetica were analyzed by cluster analysis and PLS-DA analysis ；the aggregation of samples was analyzed and determined the primary difference components. RESULTS：The linear range of polyphyllin Ⅱ，polyphyllin Ⅵ and polyphyllin Ⅶ were 0.051-2.04，0.007-0.28，0.168-6.72 μg， respectively（r≥0.999 5）；the detection limits were 1.92，1.75，1.87 ng，respectively；and the quantitative limits were 6.40，5.87， 6.23 ng，respectively；RSD of precision ，reproducibility and stability tests （24 h）were all lower than 2％（n＝6）；the average recovery rates were 99.29％，101.38％ and 99.64％，with RSDs of 1.17％，2.64％，0.75％（n＝6），respectively. The content of polyphyllin Ⅱ was 0.615-1.875 mg/g，that of polyphyllin Ⅵ was 0-0.095 mg/g，and that of polyphyllin Ⅶ was 3.158-12.354 mg/g. Cluster analysis showed that 20 batches of samples were clustered into two groups ，batch S 9-S12 were clustered in to one group，and the other 16 batches of samples were clustered into another group. PLS-DA analysis showed that 20 batches of samples were divided into 3 areas，batch S 1，S2，S8，S14，S16，S20 were included in area Ⅰ；batch S 9-S12 included in area Ⅱ；and the rest of the samples included in area Ⅲ. The quality of Y. thibetica from different habitats was different ，and there was no difference in the saponin composition between the whole grass and the underground part. Weight ranking found that mail：cscdtcm@126.com polyphyllin Ⅶ was the main difference component in Y. thibetica，and the content of polyphyllin Ⅶ in Y. thibetica from Pengzhou city and Dayi county was the highest. CONCLUSIONS ：The established method is simple ，convenient and sensitive. It can be used for the content determination of 3 saponins in Y. thibetica . The content of active components is higher and the quality is better in Y. thibetica from Pengzhou city and Dayi county.

Study on Synthesis and Anti-tumor Activity of 6 Kinds of Tectorigenin Mannich Base Derivatives / 中国药房

OBJECTIVE： To conduct structural modification of tectorigenin to search for new compounds with anti-tumor activity. METHODS： Tectorigenin was used as a lead compound， and then added into amine reagents as ethanolamine， methylamine， ethylamine， dimethylamine， diethylamine， n-propylamine and formaldehyde solution. Tectorigenin Mannich base derivatives were synthesized by mannich reaction with as the lead compound. The structures of the derivatives were identified according to IR， UV， MS and NMR data. Solubility of tectorigenin and its derivatives were investigated by solubility test method. MTT assay was used to investigate the inhibitory effects of tectorigenin and its derivatives on the proliferation of human colon cancer cell line HCT116， human lung cancer cell line A549 and human hepatoma cell line HepG2， and half inhibitory concentration （IC50） was calculated. The inhibition rate of tectorigenin and its derivatives （100 mg/kg） on H22 hepatoma-bearing mice in vivo was studied. RESULTS： Totally of 6 kinds of tectorigenin mannich base derivatives were synthesized， such as 8-（N-hydroxyethyl）-methyleneamino-5，7，4′-trihydroxy-6-methoxyisoflavone， 8-（N-methyl）-methyleneamino-5，7，4′-trihydroxy-6- methoxyisoflavone， 8-（N， N-diethyl）-methyleneamino-5，7，4′-trihydroxy-6-methoxyisoflavone， 8-（N， N-dimethyl）-methyleneamino- 5，7，4′-trihydroxy-6-methoxyisoflavone， 8-（N-ethyl）-methyleneamino-5，7，4′-trihydroxy-6-methoxyisoflavone， 8-（N-propyl）- methyleneamino-5，7，4′-trihydroxy-6-methoxyisoflavone （compounds 1-6 in turn）. Compared with tectorigenin， the water solubility of six derivatives was significantly improved， and the solubility was 5-20 times higher than that of tectorigenin. IC50 of compounds 1， 3 and 5 to HCT116 cells were （34.82±3.27）， （16.21±4.13）， （33.12±3.25） μmol/L， which were stronger than that of tectorigenin [（45.23±5.74） μmol/L]； IC50 of compounds 1， 3 and 5 to A549 cells were （37.05±5.74）， （26.88±4.52）， （30.13±6.23） μmol/L， which were stronger than that of tectorigenin [（53.24±6.34） μmol/L]； IC50 of compounds 1， 3 and 5 to HepG2 cells were （23.74±1.45）， （18.96±2.34）， （30.95±2.87） μmol/L， which were stronger than that of tectorigenin [（48.98±2.58） μmol/L]. Compounds 1， 3 and 5 showed higher inhibition rates （55.51％， 57.20％ and 49.15％） than tectorigenin （33.05％） on H22 hepatoma-bearing mice， respectively. The other three compounds had no obvious advantage over tectorigenin in anti-tumor activity. CONCLUSIONS： In this study， compounds 1， 3 and 5 of six tectorigenin mannich base derivatives synthesized in this study have stronger antitumor activity than tectorigenin.

Effects of Serglycan on Drug Resistance of Ovarian Cancer and Its Mechanism Based on Bioinformatics / 中国药房

OBJECTIVE： To study the effects of serglycan （SRGN） on drug resistance of ovarian cancer and its mechanism. METHODS： Gene expression profile interactive analysis tool （GEPIA） was used to extract related data set of ovarian cancer and analyze the difference of mRNA expression of SRGN between normal ovary tissue and ovarian cancer tissue. Gene expression database （GEO） was adopted to obtain the difference of the mRNA expression of SRGN in cisplatin sensitive and cisplatin resistant cell lines （A2780）. STRING online database was used to screen proteins interacting with SRGN （confidence degree： 0.900， interactors： 10）. Adopted biological information annotation database （DAVID） to analysis Kyoto encyclopedia of genes and genomers（KEGG）metabolism pathway to predict the potential pathways of SRGN regulating drug resistance of ovarian cancer. Medical ontology information retrieval platform COREMINE was used to mine the biological processes of significant relationship of SRGN and ovarian cancer with drug resistance. RESULTS： mRNA expression of SRGN in ovarian cancer tissue was significantly higher than normal ovarian tissue （P＜0.05）. mRNA expression of SRGN in cisplatin resistant ovarian cancer was significantly higher than cisplatin sensitive ovarian cancer （P＜0.001）. 10 proteins interacting with SRGN were screened， including albumin， transforming growth factor β1， platelet factor 4， fibrinolysin and vascular endothelial growth factor A. SRGN participated in KEGG metabolism pathway of regulating drug resistance of ovarian cancer， including HIF1α pathway， cytokine-cytokine receptor pathway， coagulation and complement cascades pathway， etc. Biological processes included gene expression， cell growth， apoptosis and cell death. CONCLUSION： SRGN mediates drug resistance of ovarian cancer， which is associated with HIF1α signaling pathway and cytokine-cytokine receptor pathway.

Application of guide combined with probing the internal wall of pedicle screw trajectory for subaxial cervical pedicle screw placement / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the skill and evaluate the accuracy for application of guide combined with probing the internal wall of pedicle screw trajectory for subaxial cervical pedicle screw placement.</p><p><b>METHODS</b>Subaxial cervical pedicle screw was inserted in 11 patients by the guide combined with probing the internal wall of pedicle screw trajectory from January 2014 to October 2016, including 7 males and 4 females with an average age of 48.1 years(ranged 32 to 63 years). There were 4 cases with cervical spondylotic myelopathy, 4 with fracture and dislocation of cervical vertebrae, 1 with cervical cord injury without fracture and dislocation, and 2 with atlantoaxialfracture and dislocation. The target pedicle's diameter, optimal entry point, sagittal angle and cross-sectional angle were measured by CT before operation. During operation, the pedicle screw inserted angle was controlled by a guide with a self-designed protractor and probed the internal wall of pedicle screw trajectory as medial safety margin of insertion screw. The accuracy of cervical pedicle screw was evaluated by CT with classification of four grades and assessed whether there was injury of spine cord or vertebral artery postoperatively.</p><p><b>RESULTS</b>Seventy-one cervical pedicle screws were placed among 11 patients, and no one had been found with clinical manifestations of injury of spine cord (or nerve root) or vertebral artery after operation. According to postoperative CT scan for evaluating the grade of screw position, 52 screws were in grade 0, 13 in grade 1, 4 in grade 2, 2 in grade 3, and 91% (65/71) located in good position. In total, 6 screws were incorreted in placement, and 4 cases of them broke medial wall and 2 cases broke lateral wall.</p><p><b>CONCLUSIONS</b>The method of probing the internal wall of pedicle screw trajectory for subaxial cervical pedicle screw placement is safe and reliable, but the studying curve is long. Probing the internal wall of pedicle screw trajectory and controlling the insertion angle by guide with a protractor are key points of this technology.</p>

Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid accumulation in human L02 hepatocytes / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanol-induced lipid deposition in human L02 hepatocytes.</p><p><b>METHODS</b>L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl-tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively.</p><p><b>RESULTS</b>Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content (9.69±0.22 μg/mg protein vs. 4.93±0.49 μg/mg protein, P<0.01), and ROS formation (7254.8±385.7 vs. 5825.2±375.9, P<0.01). Meanwhile, improvements in mitochondrial membrane potential (10655.33±331.34 vs. 11129.52±262.35, P<0.05) and ATP level (1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P<0.01) were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression (P<0.01) and upregulate PPARα expression (P<0.01) in ethanol-treated cells.</p><p><b>CONCLUSIONS</b>Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPARα expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.</p>

Study on the Chemical Compositions of the Leaves of Iris tectorum / 中国药房

OBJECTIVE:To study the chemical compositions of the leaves of Iris tectorum. METHODS:Using 70% ethanol for extracting,silica gel column chromatography,Sephadex LH-20 chromatography and thin-layer chromatography were used to iso-late and purify the chemical compositions of the leaves of I. tectorum,the compound structures were analyzed and identified accord-ing to the physicochemical properties and spectral data. RESULTS:12 compounds were isolated from the leaves of I. tectorum, namely 5,7,4′-trihydroxy-6-methoxy isoflavone(1),tiliamin-7-O-β-D-glucopyranoside(2),5-hydroxy- 4′,7- dimethoxy-isofla-vone(3),tectoridin(4),tectorigenin(5),iridin(6),dimethyl tectorigenin(7),genistein(8),protocatechuic acid(9),isorham-netin-7-O-β-D- glucoside (10),daucosterol (11),tetradecanoic acid (12). CONCLUSIONS:Compounds 1,2,3 are isolated from the plants of the genus for the first time,and the study has laid the foundation for the quality evaluation of I. tectorum.

Study on the Quality Standard of Belamcandin Standard Substance / 中国药房

OBJECTIVE:To establish the quality standard of Belamcandin standard substance.METHODS:Different indices of standard Belamcandin were examined with quantitative and quantitative analyses according to the corresponding measures stipulated in the Appendix of pharmacopoeia of people's republic of China(part Ⅱ)published in 2005.RESULTS:The specific rotatory power of 3 batches of standard Belamcandin was —28?～—30?([?]25 D,c0.11,Pyridine);the E1% 1 cmwas 790～830;the melting point was 252～254 ℃ and the ash content was less than 0.5%.The content of Belamcandin in the products was above 99.5% as revealed by HPLC.CONCLUSION:All of the indices were shown to meet the standards for standard substances and the established standard can be used for the quality control of standard Belamcandin.