This paper presented the conventional methods for signal detection of adverse drug reactions (ADRs) and their applications, the research progress in ADRs signal mining based on healthcare big data, and briefed the methods and uses of ADRs prediction using machine learning technology in the era of healthcare big data.The conclusion was that deep learning, as a fast growing tool in machine learning, will become hotspot of research, expected to help with ADRs signal mining and rational clinical drug use.

Purpose　To describe clinicopathological and immunophenotypic features of 10 cases of histiocytic necrotizing lymphadenitis (HNL). Methods　HE sections of 11 lymph node biopsies were re-examined. Immunophenotyping and detection of apoptotic DNA fragments were performed using S-P and TUNEL methods, respectively. Results　Five cases have been diagnosed as non-Hodgkin lymphoma. Histologically variable-sized discrete or confluent nodules were seen in the paracortex, especially in the interfollicular area, which were composed of proliferative pleomorphic histiocytes, transformed lymphocytes, and karyorrhectic debris. Immunohistochemistry revealed CD3+ and CD45RO+ for lymphocytes, Mac387+ and/or CD68+ for histiocytes, and no expression for CD15,CD30 and CD20 in the lesions. Conclusions　The presence of pleomorphic histiocytes, transformed T-cells, and karyorrhectic debris in the biopsy of lymph nodes, together with the absence of neutrophils support the diagnosis of HNL.

Objective To understand non stomatology undergraduates'strategies for learning stomatology and to study the reform on this course.Methods The learning strategies of 560 undergraduates majoring in clinical medicine from grade 2007 were investigated s and ten related factors like learning attitudes were investigated by learning strategies scale.Correlation analysis and linear regression analysis were applied to deal with research data.Results Most undergraduates were lack of strategies in learning stomatology.Related coefficient between 10 factors and academic scores ranged from 0.197 to 0.401,existing positive correlation(P＜0.05).Determination coefficients(R2)of attitude,motivation,time management and learning auxiliary means were 0.146,0.167,0.223and 0.122 respectively,which can be used to predict the scores of examination.Condusions Non stomatology undergraduates'strategies for learning stomatology is a vital factor influencing their academic scores.It's necessary for teachers to improve their teaching methods considering students'professional characteristics and learning strategies.

Objective To study the effects of matrine (MAT) on the apoptosis and the expression of PEG10 in human hepatocarcinoma cell line HepG2. Methods MTT assay was used to determine the proliferation-inhibition activity by MAT to HepG2 cell. JC-1 staining was prepared to detect the change of mitochondrial membrane potential in HepG2 cells after MAT was given. RT-PCR and immunocytochemical method for detecting the PEG10 gene and protein expression levels were used. Results MAT could inhibit the HepG2 cell proliferation above the concentration of 0.125 mg/mL (different from above-->MAT ≥ 0.1 g/L) and in a concentration-dependent and time-dependent manner(P<0.01). JC-1 staining and flow cytometry detection showed that MAT can significantly decrease the mitochondrial membrane potential of HepG2 cells (P < 0.01). The RT-PCR and immunocytochemical staining results showed that 0.5 and 2.0 mg/ml (different from Chinese) MAT could reduce PEG10 gene and protein expression obviously. Conclusion MAT could decrease the expression level of PEG10 gene and inhibited cell proliferation,change the mitochondrial membrane potential and induce HepG2 cell apoptosis.

Objective To investigate the effect of cerebral ischemia on functional parameters of affected arteries and probe into the possible pathogenesis of ischemia-reperfusion injury.Methods Intraluminal suture ischemic model was used by occlusion of left middle cerebral artery in rats.Two hours later,the middle cerebral artery segments were isolated from both ischemia and control groups for measurement of changes in vessel diameter induced by increasing pressure and vasoactive compounds.And then,distensibility,myogenic tone,reactivity to 5-HT and ACh were calculated and compared between groups.Results In lower pressure range,ischemic vessels showed an increased myogenic tone(at 40 mm Hg,1 mm Hg=0.133 kPa,19.3%±0.4% vs 10.0%±0.2%,t=20.568,P=0.000)and decreased diameter.In higher pressure range,ischemic vessels showed an increased diameter.distensibility and decreased myogenic tone(at 120 mm Hg,12.0%±0.2% vs 21.8%±0.4%,t=-23.575,P=0.000).In normal pressure range,myogenic tone was not altered after ischemia. Both groups constricted to 5-HT and dilated to ACh,however,the response was significantly diminished after ischemla.Conclusion These findings demonstrate that contractile and diastolic function of affected artery was impaired after ischemia,a result that may contribute to ischemia-reperfusion injury by losing upstream cerebrovascular resistance and increasing perfusion on the microcirculation.

OBJECTIVETo study the expressions of gastric mucosal proteins in chronic gastritis (CG) rats of Pi-Wei damp-heat syndrome (PWDHS), to investigate the pathogenesis correlated to CG rats of PWDHS, to observe the differential expressions of gastric mucosal proteins in CG rats of PWDHS, and to investigate the mechanisms of Sanren Decoction (SD) for treating CG rats of PWDHS.

METHODSTotally 36 male SD rats were adaptable fed for 3 days and randomly divided into 3 groups, i.e., the normal control group, the CG of PWDHS rat model group (abbreviated as the model group), and the SD treatment group, 12 in each group. The CG of PWDHS rat model was prepared by composite factors. The gastric mucosal protein was separated using two-dimensional gel electrophoresis technique, and stained by Coomassie brilliant blue. The protein spots expressed differently were analyzed by PDquest 8.0 software. The protein spots expressed differently was identified by MALDI-TOF/TOF-MS.

RESULTSThe protein spots were 1 025 +/- 3 9, 994 +/- 51, 1 087 +/- 33 in the normal control group, the model group, and the SD treatment group respectively detected from two-dimensional gel electrophoresis profiles. Compared with the normal control group, there were 74 protein spots differentially expressed in the model group, 30 spots up-regulated and 44 spots down-regulated. Compared with the model group, there were 75 protein spots differentially expressed in the SD treatment group, 49 spots up-regulated and 26 spots down-regulated. Five protein spots differentially expressed were successfully identified, i.e., heat shock protein 72 (HSP72), heat shock protein 60 (HSP60), protein disulfide-isomerase (PDI), malate dehydrogenase (MDH), and unnamed protein.

CONCLUSIONSThe pathogenesis of CG of PWDHS may be correlated to energy metabolism disturbance and stress. The mechanisms of SD for treating it may possibly adjust differential expressions of gastric mucosal proteins.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; metabolism ; Gastritis ; diagnosis ; drug therapy ; metabolism ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Proteome ; metabolism ; Rats ; Rats, Sprague-Dawley

Adverse drug reaction(ADR)reports are acting as primary sources for post-marketing drug safety evaluation, which have important reference value for drug safety evaluation. In this article, bidirectional gated recurrent unit, a kind of deep learning method, was applied as the model for relation extraction of drugs and adverse reactions in free-text section of ADR descriptions in Chinese ADR reports, with attention as well as character embedding and word segmentation embedding added into the network. The experimental results showed that our model achieved good performance in the classification task of confirming the relationship of “Drug-ADR” pair(denial, likely, direct and post-therapy)in the ADR description, and the final model achieved an F-value of 87. 52%. The extracted information can assist in evaluating ADR reports and at the same time be utilized in tasks like statistical analysis of certain drugs and adverse events and ADR knowledge base construction to provide more research techniques for drug safety researches.

This study was aimed to explore the effects of oleanolic acid on PTEN expression and apoptosis of Jurkat cells. The inhibitory rate was measured by Cell Counting Kit-8. The apoptotic nucleus morphous was observed by Hoechst 33258 staining. The apoptosis rate of Jurkat cells were determined by flow cytometry with Annexin V/PI double staining. PTEN mRNA and protein were detected by quantitative real-time PCR and Western blot respectively. The results showed that oleanolic acid inhibited the proliferation of Jurkat cells in time- and dose-dependent manners. The 50% growth inhibition (IC(50)) at 12, 24 and 48 hours were about 85.35 µmol/L, 53.66 µmol/L and 33.18 µmol/L respectively. Flow cytometric assay showed that the apoptotic rates of Jurkat cells treated with oleanolic acid (0, 40, 80 and 160 µmol/L) for 24 hours were 6.72%, 19.8%, 28.72% and 30.12% (p < 0.05). PTEN mRNA and protein expressions were up-regulated in Jurkat cells treated with oleanolic acid of concentration 80 µmol/L and 160 µmol/L for 24 hours. It is concluded that up-regulation of PTEN mRNA and PTEN protein may be involved in oleanolic acid-induced Jurkat cell apoptosis.
Apoptosis ; drug effects ; Cell Proliferation ; Humans ; Jurkat Cells ; Oleanolic Acid ; pharmacology ; PTEN Phosphohydrolase ; metabolism ; Up-Regulation

OBJECTIVETo investigate the effect of RNA interference (RNAi)-mediated silencing of the SREBP2 on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells.

METHODSShort-hairpin (sh)RNA targeting SREBP2 or negative control (NC) shRNA were transfected into HepG2 cells by a liposomal method. G418-selective culturing was used to obtain the SREBP2 shRNA HepG2 and NC shRNA HepG2 cell lines. The two cell lines were cultured in serum-free medium and left untreated (control) or treated with TNF-a (20 ng/ml), low-density lipoprotein (LDL) loading (100 mug/ml), or a combination LDL plus TNF-a treatment. Lipid accumulation was evaluated by oil red O (ORO) staining. Intracellular cholesterol level was measured by enzymatic assay. The mRNA and protein levels of SREBP2 and its downstream target genes, LDL receptor (LDLr), and HMGCoA reductase, were measured by real-time PCR and Western blotting, respectively.

RESULTSSREBP2 shRNA HepG2 and NC shRNA HepG2 stable cell lines were successfully established. ORO staining and cholesterol quantitative analysis showed that LDL loading significantly increased intracellular cholesterol and that expression of SREBP2 further exacerbated the inflammatory cytokine-induced lipid accumulation, as seen in NC shRNA HepG2 cells. LDL loading of NC shRNA HepG2 decreased the gene and protein expressions of SREBP2, LDLr, and HMGCoA reductase, but the suppressive effect was overridden by inflammatory cytokine. SREBP2 shRNA HepG2 cells showed lower levels of cholesterol accumulation under LDL loading and inflammatory stress conditions. Moreover, the mRNA and protein levels of SREBP2, LDLr, and HMGCoA reductase were much lower than in NC shRNA HepG2 cells under the same conditions.

CONCLUSIONInflammatory cytokine exacerbated cholesterol accumulation in HepG2 via disrupting SREBP2. RNAi-mediated inhibition of SREBP2 expression significantly ameliorated the cholesterol accumulation induced by inflammatory cytokine.

Cholesterol ; metabolism ; Hep G2 Cells ; Humans ; Inflammation ; RNA Interference ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 2 ; genetics ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment.

METHODSFifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test.

RESULTSThe baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05).

CONCLUSIONHBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult