OBJECTIVE Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that has been newly identified. It promotes tumor proliferation and invasion via the MET pathway. Our study investigated the effects of Saikosaponin-b(SS-b) on the proliferation and apoptosis of HepG2 cells and its regulation on MACC1/c-Met/Akt signaling pathway. METHODS HepG2 cells were treated with SS-b (10-800 g·L-1) for 48 h in vitro. The CCK-8 assay was used to assess cell proliferation, and cell apoptosis was determined by Hoechst33258 staining, AnnexinⅤ/PI staining and caspase 3 assay. RT-PCR was used to examine the expression of MACC1, c- MET and hepatocyte growth factor (HGF) mRNA. MACC1 protein was detected by Western blot and immunohistochemistry. The protein expressions of p-c-MET, c-MET, p-AKT, AKT, p-BAD, BAD were measured by Western blot. RESULTS SS-b inhibited the growth of HepG2 cells in dose-dependent way and induced cell apoptosis significantly. HepG2 cells showed karyopyknosis, fragmentation and fluorescence highlight in SS-b treatment group. FCM results showed that apoptosis rate of HepG2 cells increased with SS- b concentration. The immunofluores?cence results showed that the MACC1 expression decreased significantly in HepG2 cells treated with SS-b. The expression levels of MACC1, c-MET and HGF mRNA in HepG2 cells were significantly inhibited by SS-b. SS-b also significantly decreased the protein expressions of MACC1, p-c-MET and p-AKT while increased the expression of p-BAD and caspase 3 in HepG2 cells(P<0.05). CONCLUSION SS-b inhibited the proliferation and induced the apoptosis of HepG2 cells by targeting the MACC1/c-Met/Akt signaling pathway.

OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma (HCC). In this study, we investigated the anti-proliferative activities and anti-angiogenesis effects of saikosaponins (SS)-b on hepatocellular carcinoma (HCC) and its regulation on VEGF/ERK/HIF-1α signal pathway. METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro. Pathological change of tumor tissue was observed by HE staining, the microvascular changes were detected by immunohistochemical method. The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane (CAM) model. The effects of SS- b on proliferation, migration and invasion were investigated by MTT assay, scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell (HUVEC) and HepG2 cells in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-2/9(MMP-2/9), hypoxia-inducible factor-1α (HIF-1α) expression and the phosphorylation of extracellular regulated kinase(ERK) were analyzed using RT-PCR and Western-blot. RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo. The inhibitory rate of tumor was 49.1%, 50.7%, 66.1% in SS-b 5, 10 and 20 mg·kg-1 group respectively. HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice. Moreover, SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF. SS-b had an obvious inhibitory effect on cell proliferation, migration and invasion of HUVEC cells and HepG-2 cells. These effects were associated with down-regulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1α signaling in H22 mice and Hep-G2 cells. CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibit?ing tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.

Objective To investigate the relationship between epidermal growth factor receptor (EGFR) gene mutation and computed tomography (CT) features and clinical features in non-small cell lung cancer (NSCLCs) patients. Methods The clinical data of 187 patients with NSCLCs admitted in our hospital from September 2014 to July 2016 were retrospectively analyzed. All the patients accepted the EGFR mutated gene detection, and they were divided into effective mutation group (n=67) and non-effective mutation group (n=120). The clinical data and lung CT imaging data were complete in the two groups. The univariate and multivariate Logistic regression analysis were used to analyze the differences of imaging and clinical features between the two groups. Results Comparing with the non-mutation group, there were higher proportion of women and lower smoking index in the EGFR effective mutation group. Lesions in the lung tissue showed a clear edge, leaf and burr, and containing ground-glass opacity (GGO) component, usually accompanied by airway bronchogram and pleural indentation, and associated with cancer lymphatic inflammation and lung metastasis in mutation group (all P < 0.05). There were no significant differences in the proportion of necrosis, cavitation, calcification, halo sign and vacuole sign between the two groups (P > 0.05). Logistic regression analysis showed that female, GGO containing composition, burr, air bronchogram, carcinomatous lymphangitis and lesion density showed obvious airway involvement were the predictive risk factors in patients with EGFR effective mutation. Conclusion The EGFR mutation occurs more oftern in female. The reliable predictive signs of CT include GGO composition, burr, airway bronchogram and carcinoid lymphangitis. In critical patients who are not easy to obtain clinical pathology, it has a guiding significance to radiographic assessment for EGFR effective mutation.

Objective:To analyze the main inputs and outputs of China's health reform,to propose suggestion on improving health policy.Methods:Using health economics input and output analysis methods.Results:From 2009 to 2016,more than 50％ of Chinese health personnel were distributed in the hospital and increased by year,more than 70％ of the government's main health expenditure were paid for disease treatment,the total number of new patients was 2.44 billion,and the number of inpatients was 100 million.The actual medical burden of individual residents in China was 49.36％ in 2016.The prevalence of chronic diseases among residents increased by 9％ from 2008 to 2013.Conclusion:China should put more new health investment and resources into disease prevention and control,so as to improve the health level and health input and output performance of residents.

In order to investigate the molecular evolution and spatio-temporal migration of Getah viruses (GETV) isolated around the world,the nucleotide and deduced amino acid sequence of GETVs were analyzed and phylogenetic trees were constructed by using informatics software including ClustalX1.83,MegaAlign,GeneDOC and Mega6.0.The Bayesian Stochastic Search Variable Selection (BSSVS) program in the BEAST v 1.8.1 software package was used to analyze the spatial dynamics of the Getah virus.Results showed that the full-length of Getah virus E2 gene consists of 1 266 nueleotides,encoding 422 amino acids.And the homology of nucleotide and amino acid were 94.5％ 100％ and 96.4％ 100％ respectively.The molecular evolution analysis revealed that there were no species and geographical distribution difference existing among GETV host animals (e.g.horses and pigs) and vectors (e.g.mosquitoes).Bioinformatics analysis showed that GETV originated in Malaysia,then it was spread to Japan,China,South Korea,Mongolia,Russia,etc.GETV E2 gene was relatively stable since GETV was first isolated in 1955.The differences of species and geographical distribution did not exist among GETV host animals and vectors,and the virus has spread from tropical regions to Eurasian continent.Thus,strengthening the detection and monitoring of GETV and its infections in humans and livestock is critical.

Objective:To prepare loratadine nanosuspension lyophilized powder (LTD-NLP) and investigate the dissolution and stability. Methods:LTD-NLP was prepared by an anti-solvent precipitation method; the particle size and morphology were characterized by a laser nanometer particle sizer and a transmission electron microscope (TEM). The optimal lyophilized protective agent was screened out; the dissolution and stability of LTD-NLP were determined by HPLC. Results:The average particle size of LTD-NLP was 175.6 nm with PDI of 0.200, and the zeta potential was -56.3 mV. The shape of LTD-NLP was spherical. The nanosuspension lyophilized with 10% sucrose presented optimal properties. The dissolution of LTD-NLP was greater than raw material, and LTD-NLP had good stability at 4℃. Conclusion:The anti-solvent precipitation method for LTD-NLP is simple,and the product is expected to become a new preparation of loratadine.

Objective To evaluate the effects of different target plasma concentrations of propofol on ventricular repolarization in elderly patients.Methods Forty-five patients,aged 65-80 yr,weighing 43-85 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective surgery under general anesthesia,were divided into 3 groups (n=15 each) using a random number table:propofol at target plasma concentration of 2 μg/ml group (group P1),propofol at target plasma concentration of 3 μg/ml group (group P2) and propofol at target plasma concentration of 4 μg/ml group (group P3).Before induction of anesthesia (T1) and at 5 min after propofol reached the target plasma concentration (T2),12-lead electrocardiogram was recorded,the QT and Tp-e intervals were measured,and the corrected QT (QTc) interval and Tp-e/QT ratio were calculated.Results There were no significant differences in QTc interval,Tp-e interval or Tp-e/QT ratio at T1,2 between the three groups (P＞0.05).Compared with those at T1,the QTc and Tp-e intervals were significantly shortened and the Tp-e/QT ratio was decreased at T2 in P1 and P2 groups,and the Tp-e interval was shorten and the Tp-e/QT ratio was decreased at T2 (P＜ 0.05),and no significant change was found in the QTc interval at T2 in group P3 (P＞0.05).Conclusion Propofol at clinically relevant concentrations can shorten the ventricular repolarization in elderly patients.

BACKGROUNDAtopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.

METHODSHaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.

RESULTSIL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.

CONCLUSIONSOur results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

Caspase 14 ; metabolism ; Cell Line, Tumor ; Cells, Cultured ; Dermatitis, Atopic ; metabolism ; Humans ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Keratinocytes ; enzymology ; metabolism ; Proteinase Inhibitory Proteins, Secretory ; metabolism ; Serine Peptidase Inhibitor Kazal-Type 5 ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

The structure of fibrauretin made by our lab was modified. Fibrauretin was demethylated at 9-site under high temperature pyrolysis at 160℃-180℃ and was reacted with a series of acid chlorides. Twele derivatives of fibrauretin were obtained. The structure of each derivative was determined by1H-NMR and13C-NMR. The derivatives were 9-O-benzoyl-fibrauretin, 9-O-( 2-methylbenzoyl)-fibrauretin, 9-O-( 4-methylbenzoyl)-fibrauretin, 9-O-(3, 5-dimethylbenzoyl)-fibrauretin, 9-O-(4-(chloromethyl) benzoyl)-fibrauretin and other derivatives. The 12 derivatives are all new chemical compounds. Taking ATCI as substrate,the inhibitory activity on acetylcholinesterase (AChE) from the head of flies of the fibrauretin and its derivatives were screened. The results showed that most of the derivatives had improved their inhibitory activity on AChE through esterification reaction. Compounds 9-O-(4-methylbenzoyl)-fibrauretin, 9-O-(3,5-dimethylbenzoyl)-fibrauretinand 9-O-(4-(chloromethyl)benzoyl)-fibrauretin had significant inhibitory effect on AChE,and the inhibitory activity was stronger than the that of donepezil.

The medical records of 11 pediatric patients undergoing resection of adrenal cortical carcinoma from January 2012 to January 2019 in our hospital were collected.Anesthesia management for resection of adrenal cortical carcinoma in children was analyzed and investigated.Anesthesia was induced by intravenously injecting atropine 0.01 mg/kg, dexamethasone 2-5 mg, propofol 2-3 mg/kg, sufentanil 0.3-0.5 μg/kg or fentanyl 1-2 μg/kg, rocuronium 0.5 mg/kg or cis-atracurium 0.1-0.2 mg/kg.Radial artery catheterization and femoral vein catheterization were performed under ultrasound guidance.Arterial blood pressure was continuously monitored.The esophageal thermometers probe was placed to continuously monitor body temperature.The catheter was placed to monitor urine volume.Intermittent positive pressure ventilation was performed after endotracheal intubation with the inspiratory oxygen fraction set 60%-100%, oxygen flow rate 2-3 L/min, tidal volume 7-10 ml/kg, ventilation frequency 20-26 times/min, inhalation/respiration ratio 1∶(1.5-2.0) and airway pressure 16-20 cmH 2O, and the end-tidal pressure of carbon dioxide was maintained at 35-45 mmHg.Anesthesia was maintained by inhaling 2%-4% sevoflurane and/or intravenously infusing propofol 0.10-0.15 mg·kg -1·min -1, and continuously infusing remifentanil 0.2-0.5 μg·kg -1·min -1.Hemodynamics was maintained within the normal range, and the bispectral index was maintained at 40-60 during the surgery.Before the tumor was completely removed, 5-10 mg/kg sodium hydrocortisone succinate was intravenously infused.At the end of the operation, sufentanil 0.75-1.00 μg·kg -1·d -1 or fentanyl 7.5-10.0 μg·kg -1·d -1 was continuously infused for postoperative analgesia until 48 h after operation.Operation was smoothly completed with stable anesthesia in all the pediatric patients.The tracheal tube was removed successfully after the operation.All children in this group were discharged from hospital and no death occurred.Anesthesia management for resection of adrenal cortical carcinoma required an appreciation of the clinical characteristics and perioperative pathophysiological changes.Paying attention to the changes in hormone levels during perioperative period and timely adjusting the children′s internal environment to maintain the stability of anesthesia and reduce the stress response were the keys to anesthesia management.