Objective:To explore the application effect of "blended learning + flipped classroom" in public elective courses for medical students, and provide reference for the blended construction of related courses.Methods:Totally 229 medical students were selected as research participants, who were taught by "blended learning + flipped classroom". After the courses, the curriculum evaluation questionnaires and focus group interview were used to collect students' evaluation of this course. SPSS 22.0 statistical software was used to make descriptive statistics on the questionnaire data.Results:Totally 98.5% students preferred "blended learning + flipped classroom" teaching mode, and more than 93% students thought this teaching method could improve their learning interest, empathy, understanding and application of knowledge. The results of the qualitative survey extracted two themes, namely "improving learning autonomy" and "expanding comprehensive quality".Conclusion:Perfecting the "blended learning + flipped classroom" teaching mode of the medical public elective courses plays a positive role in improving the learning autonomy and comprehensive quality of medical students and optimizing the learning effect.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To investigate relationships between social support and dysfunctional cognition, personality disorder in patients with somatoform disorder.Methods:One hundred and four patients with somatoform disorders and 97 healthy subjects were evaluated with the Social Support Rating Scale (SSRS), Dysfunctional Attitudes Scale (DAS) and Personality Diagnostic Questionnaire (PDQ-4). Social support ratings were compared between patients and healthy controls.The relationship between social support and dysfunctional cognition, personality disorder were analyzed.Results:The scores of social support in all dimensions of patients with somatoform disorder(total score of social support(37.18±8.12), objective social support(8.49±2.83), subjective social support(21.90±5.44), social support utilization(6.79±1.85)) were significantly lower than those in the healthy control group(total score of social support(41.82±6.87), objective social support(9.92±3.38), subjective social support(24.32±4.25), social support utilization(7.59±1.31))( P<0.05). In patients with somatoform disorder, there was a significant negative correlation between the total score of SSRS and the scores of DAS ( r=-0.245, P<0.05) and personality disorder tendency ( r=-0.292, P<0.01). Social support utilization had a significant predictive effect on dysfunctional cognition ( B=-5.384, P=0.007). Conclusion:Social support of patients with somatoform disorder is correlated with dysfunctional cognition and personality disorder tendency, which provides the basis for psychological intervention such as group and family psychotherapy.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

To further explore an efficient strategy for the construction of antitumor fluoroquinolone molecules from antibacterial fluoroquinolone drugs, twelve new title compounds, 1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-(3-substituted-rhodanin-5-ylidene)methyl-quinolon-4(1H)-ones(6a-6l), was designed and synthesized with α, β-unsaturated ketone scaffold and a rhodanine ring as an isostere and fused modified group, respectively, from pefloxacin(1), and their structures were characterized by elemental analysis and spectral data. The in vitro anti-cell proliferative activity of the title compounds against the tested A549, Hep-3B and HL60 cancer cells exhibited more significant potency than parent 1. In particular, halogenated phenyl title compounds(6d, 6e, 6f)displayed a comparable activity to comparison doxorubicin against A549 cells and low cytotoxicity against normal Vero cells. Thus, a methylene rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group have shown to be beneficial to improving the antitumor activity.

Objective: To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI). Methods: The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI. Results: MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01). Conclusions The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

BACKGROUND:Inflammatory factor plays an important role in restenosis after bal oon injury. Sphingosine1-phosphate receptor 1 can enhance the expression of inflammatory factor and promote development and progression of this pathological process.
OBJECTIVE:To observe the expression of the inflammatory factors and sphingosine1-phosphate receptor 1 after bal oon injury of the rat carotid artery and effects of fingolimod hydrochloride on reducing inflammatory reaction.
METHODS:Sixty Sprague-Dawley rats were equal y and randomly divided into four groups. In the blank control group and negative control group, left common carotid artery was only isolated, and left external carotid artery was ligated. In the bal oon injury group and drug intervention group, rat models of carotid artery injury were
established by bal oon injury on the left common carotid artery. In the negative control and drug intervention groups, the rats were intraperitoneal y injected with fingolimod hydrochloride 1 mg/kg. In the blank control and bal oon injury groups, the rats were intraperitoneal y injected with an equal volume of saline. Samples were col ected at 3, 7 and 21 days.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that the proliferation of blood vessel was remarkable in the bal oon injury group, but attenuated in the drug intervention group. The appearance of blood vessels was normal in the blank control group and negative control group. Real-time fluorescent quantitative PCR revealed that cyclooxygenase 2 and prostaglandin E2 mRNA expression levels were significantly lower in the drug intervention group than those in the bal oon injury group at 7 days (P<0.05). Cyclooxygenase 2 and prostaglandin E2 mRNA expression levels were significantly higher in the bal oon injury group and drug intervention group than those in the blank control group and negative control group at the same time point (P<0.05). Western blot assay results revealed that sphingosine1-phosphate receptor 1 expression was high in early stage of injury, and then reduced in late stage of injury. In particular, protein expression further decreased after drug intervention. Results indicated that fingolimod hydrochloride suppressed inflammatory reaction of injured blood vessels and lessened the stenosis of injured blood vessels by regulating cyclooxygenase 2 and prostaglandin E2 mRNA expression using sphingosine1-phosphate receptor 1.

OBJECTIVETo investigate the mechanisms of Wuling mycelia powder on memory retrieval impairment in rats with chronic epilepsy.

METHODSD rats were randomly divided into four groups: the pentylenetetrazole-kindling group (the model control group), the low dose of Wuling mycelia powder (0.3 g x kg(-1), ig) group, the high dose of Wuling mycelia powder (0.6 g x kg(-1), ig) group and the blank control group. After being successfully trained in the 8-arm (4-arm baited) radial maze, the rats were intraperitoneally injected with a subconvulsive dose (35 mg x kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for 12 times. Wuling mycelia powder were orally administered 30 min before every pentylenetetrazole injection. Memory retrieval was tested at the same maze. Phosphorylated CREB were analyzed by Western blot. Brain pathological sections were stained using HE, hippocampal nerve cells were observed under optical microscopes.

RESULTBoth of reference and working memory abilities of these chronic epilepsy rats were impaired as expressed in the 8-arm radial maze but reversed by Wuling mycelia powder to some extent. Chronic epilepsy caused a decreasing p-CREB in hippocampal nerve cells and injury in hippocampal CA1 region and CA3 region among rats. Wuling mycelia powder inhibited hippocampal p-CREB from decreasing and protected hippocampal nerve cells.

CONCLUSIONWuling mycelia powder could ameliorate memory impairment induced by epilepsia. Its mechanism may be related to the increase in p-CREB expression in brain and the protective effect on hippocampal nerve cells.

Animals ; Chronic Disease ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epilepsy ; complications ; Hippocampus ; drug effects ; pathology ; Male ; Memory Disorders ; drug therapy ; Phosphorylation ; Rats ; Rats, Sprague-Dawley

BACKGROUND AND OBJECTIVEIt ha been proven that serum vascular endothelial growth factor (VEGF) concentration was elevated significantly after surgery in patients of non-small cell lung cancer (NSCLC). Platelet may be the main resource of serum VEGF. The aim of this study is to investigate the correlation between postoperative dynamic changes of serum VEGF levels and platelet counts in patients of NSCLC who underwent surgery.

METHODSSerum VEGF levels were determined in 76 patients of NSCLC who were treated with surgery by ELISA (enzyme linked immunosorbent assay) method before operation and on postoperative day 1, 7. At the same day the concentrations of platelet were determined. RESULTS (1) Serum VEGF in patients of NSCLC on preoperative day, postoperative 1 day and 7 day were (842.06 +/- 527.24) pg/mL, (1 119.28 +/- 609.62) pg/mL, (1 574.09 +/- 873.38) pg/mL, respectively (P < 0.001); (2) Platelet counts in patients of NSCLC on preoperative day, postoperative 1 day and 7 day were (230.42 +/- 82.56 x 10(9)/L, (196.47 +/- 81.48) x 10(9)/L, (237.90 +/- 86.94) x 10(9)/L; the value on postoperative 1 day was the lowest (P < 0.001); (3) On postoperative 7 day, serum VEGF in the group of lower than the mean and higher than the mean were respectively (1 398.81 +/- 734.00) pg/mL and (1 842.86 +/- 1 006.63) pg/mL (P = 0.043).

CONCLUSIONSerum VEGF in patients of NSCLC after surgery were elevated. In the group of higher platelet counts, serum VEGF increased more significantly.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; surgery ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lung Neoplasms ; blood ; surgery ; Male ; Middle Aged ; Platelet Count ; Postoperative Period ; Vascular Endothelial Growth Factors ; blood

OBJECTIVETo investigate the effect of Fuzheng Huayu decoction (FHD) intervention on hepatic fibrosis.

METHODSWistar rats were randomly divided into 3 groups: rats in the normal group only treated with subcutaneous injection of saline, rats in the model group and the FHD group were made into hepatic fibrosis by subcutaneous injection of 40% carbon tetrachloride (CCl4)-olive solution and then those in the FHD group were treated with FHD by gastric perfusion after modeling. Liver samples of the rats were obtained for routine pathological observation, hydroxyproline determination and proteome quantitative determination. After then, the proteome profile was obtained through 2-dimensional electrophoresis and silver staining, and analyzed. More than 30 proteins with different expression were identified by MALDI-TOF-MS.

RESULTS(1) The integral response of vital movement such as body weight and activity of hepatic fibrosis declined in the CCl4 induced liver fibrosis rats; (2) Liver fibrosis were associated with abnormal metabolism; (3) There were four material metabolism-related protein showed by hepatic proteome mass spectrography, which expressed different between the normal and the fibrotic rats, i. e. the perchloric acid soluble protein, the phosphatidylinositol transferase, the phosphoglycerate kinase and the endoplasmic reticulum-60 protease; (4) The expressions of the above-mentioned four proteins in the FHD group were nearly the same as those of normal level.

CONCLUSION(1) Liver fibrosis is accompanied with abnormal protein synthesis and decomposition, as well as the enhanced activity of glycolysis; (2) The existence of metabolism-related proteins is one of the elements for the liver in regulating metabolism; (3) The regulation on the expressions of metablism-related proteins is one of the pathways for FHD to exert its anti-hepatic fibrosis effect.

Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; metabolism ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; Male ; Phosphoglycerate Kinase ; metabolism ; Phytotherapy ; Proteins ; metabolism ; Random Allocation ; Rats ; Rats, Wistar