Objective To investigate the effect of PBL combined with EBM applied in the teaching of fever of unknown origin. Methods PBL combined with EBM teaching was applied in fever of unknown origin course for 30 clinical medicine specialty(eight years) students of Tongji class of grade 2009(experiment group), while PBL teaching was applied in fever of unknown origin course for 30 clinical medicine specialty (eight years) students of Tongji class of grade 2008 (control group). After teaching, the theory examination for both basic knowledge and case analysis was organized for all students of both groups. At the same time the questionnaire survey was conducted to 30 students of grade 2009 to evaluate the teaching effect. The results were assessed by using SPSS 18.0 statistical software for the T-test of the experimental group and the control group.Inspection level was α=0.05. Results The theory test score of students in the experimental group was (93.5±3.2) point, signifi-cantly higher than that of the students in the control group(84.7±2.8). There was statistically signifi-cant difference between the scores of the two groups of students (P=0.00). Survey results showed 19 students ( 63 . 33%) thought that the development of PBL teaching combined with evidence-based medicine teaching had its necessity, and 16 students(53.33%) thought that the teaching method im-proved their clinical thinking ability of logical reasoning. Conclusion The concept of PBL combined with EBM has achieved significant resultsinthe teaching offever of unknown origin, and it is necessary to carry out this teaching mode in medical colleges with certain teaching strength.

Objective: To evaluate the therapeutic efficacy of gonadotropin-releasing hormone analogues (GnRHa) in protecting ovarian function of premenopausal breast cancer patients undergoing chemotherapy. Methods: The randomized controlled trials of GnRHa protecting ovarian function of premenopausal breast cancer patients undergoing chemotherapy were collected from PubMed, Cochrane Library, EMbase, China National Knowledge Infrastructure (CNKI) and Wanfang Databases, and the date range was from the establishment of the databases to March 2018. According to the inclusion and exclusion criteria, the literatures about amenorrhea rate, premature ovarian failure (POF) rate, menstrual recurrence rate, pregnancy rate, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in premenopausal breast cancer patients after chemotherapy combined with GnRHa or chemotherapy alone were screened out. The outcome measurements were odds ratio (OR) and 95% confidence interval (CI). The Meta-analysis was performed using RevMan 5.3 software. Results: A total of 17 randomized controlled trials involving 1 590 patients were included in this Metaanalysis. As compared with chemotherapy alone, the chemotherapy combined with GnRHa increased the amenorrhea rate during chemotherapy (OR = 11.14, 95% CI: 4.83-25.72, P < 0.000 01), reduced the POF rate (OR = 0.35, 95% CI: 0.25-0.50, P < 0.000 01), while improved the menstrual recurrence rate (OR = 2.90, 95% CI: 1.88-4.49, P < 0.000 01) and pregnancy rate (OR = 1.81, 95% CI: 1.08-3.02, P = 0.02). Moreover, three studies showed that the levels of FSH and LH in chemotherapy combined with GnRHa group were lower than those in chemotherapy alone group, and there were significant differences in two studies (both P < 0.01). Conclusion: Chemotherapy combined with GnRHa can increase the menstrual recurrence rate and pregnancy rate of premenopausal breast cancer patients after chemotherapy, suggesting that GnRHa has a protective effect on ovarian function of those patients.

ObjectiveTo evaluate the biological characteristics of rat bone marrow mesenchymal stem cells (BMSCs) transfected with hypoxia-inducible factor-1α(HIF-1 α) gene.MethodsThe rat BMSCs of 3rd generation and the vector expressing HIF-1α gene (pcDNA3.1-HIF-1α) were provided by department of anesthesia,Tangdu Hospital,the 4th Military Medical University.BMSCs expressing HIF-1α gene (BMSCs-HIF-1α cells) were constructed by transfection of vector pcDNA3.1-HIF-1α into BMSCs by means of electroporation.Successful transfection of HIF-1α gene was confirmed by immuno-cytochemistry.Simple BMSCs and BMSCs-pcDNA3.1 cells were used as control cells.After being cultured in hypoxic condition HIF-1α expression was detected by Western blot analysis.Flow cytometry was used to determine the proportion of cells in G1,G2 and S phase and detect apoptosis.The proliferation index (PI) was calculated.The cell growth curve was described by MTT assay and the number of the 3 types of cells was recorded.ResultsA large number of deep blue granules were observed in the nuclei of BMSCs-HIF-1α cells using immuno-cytochemistry but no such granule was found in the two types of control cells.HIF-1α expression was significantly up-regulated and apoptosis rate (the number of apoptotic cella/the total number of cells examined) decreased in BMSC-HIF-1α cells compared with the control cells.The proportion of cells in S and G2 phase was significantly higher and the proportion of cells in G1 phase was significantly lower and PI higher in BMSCs-HIF-1α cells than in the control cells.The number of BMSCs-HIF-lα cells was significantly higher than the number of the two types of control cells at day 3-8 of culture.There was no significant difference in the above variables between BMSCs and BMSCs-pcDNA3.1 cells.ConclusionBMSCs-HIF-1α is successfully constructed by transfection of vector pcDNA3.1-HIF-1α gene into BMSCs by means of electroporation.

OBJECTIVETo study the pharmacokinetics and bioavailability of ginkgolides sustained-release tablet and conventional tablet in Beagle dogs.

METHODThe concentrations of ginkgolides in plasma were determined by LC-MS. The main pharmacokinetic parameters of ginkgolides sustained-release tablet and conventional tablet in vivo were obtained using Pharmacokinetic software DAS 2.0.

RESULTThe C(max) of grinkgolide A in ginkgolide sustained-release tablet and conventional tablet were 443.51, 1 039.30 microg x L(-1), respecitvely. t(max) were 2.92, 1.08 h, respectively. AUC(0-12h) were 1 808.21, 2 041.37 h x microg(-1) x L(-1), respectively. MRT were 5.18, 3.18 h, respectively. The relative bioavailability of ginkgolides A was 88.58%. The C(max) of ginkgolide B in ginkgolide sustained-release tablet and conventional tablet were 407.13, 547.38 microg x L(-1), respectively. t(max) were 2.92, 1.08 h, respectively. AUC(01-12 h) were 1 987.31, 1 748.04 h x microg(-1) x L(-1), respectively. MRT were 6.05, 4.98 h, respectively. The relative bioavailability of ginkgolides B was 113.69%.

CONCLUSIONThe ginkgolides sustained-release tablets have good sustained release characteristics and are bioequivalent to the reference formulation.

Animals ; Area Under Curve ; Biological Availability ; Chromatography, High Pressure Liquid ; methods ; Delayed-Action Preparations ; administration & dosage ; pharmacokinetics ; Dogs ; Ginkgolides ; administration & dosage ; analysis ; pharmacokinetics ; Lactones ; analysis ; Male ; Mass Spectrometry ; methods ; Quality Control ; Tablets ; administration & dosage ; pharmacokinetics ; Therapeutic Equivalency

Objective To establish a sound and reasonable talent assessment mechanism in the introduction of scientific research talents through the reform of human resources management.Methods Based on the iceberg theory,understand better of the candidates to optimize the matching between personnel and positions.Results We proposed a multi-dimensional assessment system that combines the introduction of talents with tiered assessment of standardized talent rankings,concrete assessment will take into account of the performance and designed tasks.Established talent evaluation criteria are including moral virtues,knowledge,capacity,achievement and contributions to further improve medical ethics,clinical practice,scientific research and education training,public health services,as well as moral characteristics.Conclusions Through innovative administration,the multi-dimensional assessment system could be implemented in the introduction of scientific research talents,according to which different levels of talent will be better matched to avoid "one size fits all" or other problems.The system could also inspire the introduced talents to play a leading role in discipline development,to fulfill the strategy of strengthening hospital with talents,as well as better service for medical health.

Objective: To explore the relationship between polymorphisms of interleukin 17(IL-17) gene (rs4711998, rs763780) and the susceptibility of pneumoconiosis, and to provide a basis for prevention of high-risk groups of pneumoconiosis. Methods: A total of 219 pneumoconiosis patients and 242 workers without pneumoconiosis were enrolled in the study. All subjects were photographed with high undulating X-rays anterior chest radiographs, diagnosed according to diagnostic criteria for pneumoconiosis. We collected 3 ml of peripheral venous blood of the study subjects. Polymorphism in IL-17A rs4711998 and IL-17F rs763780 locus were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The IL-17A rs4711998 locus has AA, AG and GG genotypes, there was no the significant difference between case and control groups (P>0.05). IL-17F rs763780 had AA, AG and GG genotypes, there was a significant difference between case and control groups (P<0.05). Allele A and allele G were statistically significant difference between the case group and the control group (P<0.05). Conclusion No relationship was found between IL-17A gene polymorphisms at rs4711998 and silicosis. IL-17F rs763780 locus gene polymorphism is associated with susceptibility to pneumoconiosis. AG genotype and G allele may have a protective effect.

Objective To observe the value of radiomics models and nomogram model based on two-dimensional ultrasound and automated breast volume scanning(ABVS)for predicting molecular types of breast cancer.Methods Data of 326 female patients of single breast cancer confirmed by pathology were analyzed retrospectively.The patients were randomly divided into training set(n=260)or validation set(n=66)at the ratio of 8∶2,and further divided into Luminal subgroup and non-Luminal subgroup.Radiomics features were extracted based on two-dimensional ultrasound of breast and ABVS imaging,then model2DUS,modelABVS and modelcombined radiomics were constructed,respectively.Univariate analysis and multivariate logistic regression analysis were used to screen independent factors for predicting molecular types of breast cancer,and nomogram model(modelnomogram)was constructed combined with independent factors and radiomics Radscores.The receiver operating characteristic(ROC)curve was used to evaluate the efficacy of each model for molecular type of breast cancer.Results The maximum diameter of tumor(OR=1.029)and the retraction phenomenon(OR=0.408)were both independent predictive factors for molecular type of breast cancer(both P＜0.05).The area under the curve(AUC)of model2DUS,modelABVS.modelcombined radiomics and modelnomogram for predicting molecular type of breast cancer in validation set was 0.67,0.75,0.84 and 0.83,respectively.No significant difference of AUC of modelcombined radiomics and modelnomogram was found(P＞0.05),which were both higher than AUC of model2DUs and modelABVS(all P＜0.05).Conclusion Combined radiomics model and nomogram model based on two-dimensional ultrasound and ABVS could effectively predict molecular type of breast cancer.

OBJECTIVE: To explore the genetic basis for a child with metachromatic leukodystrophy (MLD). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Potential variant was screened by whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. The pathogenicity the variant was analyzed by multiple sequence alignment of the amino acid sequence and three-dimensional model prediction of its protein product. RESULTS: The child was found to harbor compound heterozygous variants c.257G>A (p.R86Q) and c.467del (p.G156Afs*6) of the ARSA gene, among which the c.467del (p.G156Afs*6) frameshift variation was unreported previously. Multiple sequence alignment showed that the site of the c.257G>A (p.R86Q) missense variant is highly conserved. Three-dimensional structure modeling analysis showed that the partial deletion due to the p.G156Afs*6 variant may cause significant alteration of the structure of ARSA protein. CONCLUSION The discovery of novel variant in ARSA has enriched the mutational spectrum of MLD and may facilitate the understanding of the genotype-phenotype correlation of MLD.
Cerebroside-Sulfatase/genetics* ; DNA ; Genetic Association Studies ; Humans ; Leukodystrophy, Metachromatic/genetics* ; Mutation

Objective:To evaluate the effect of sitagliptin on the expression of airway mucin 5AC (MUC5AC) in mice with endotoxin-induced lung injury.Methods:Thirty-six healthy male SPF C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), endotoxin-induced lung injury group (group L), and endotoxin-induced lung injury+ sitagliptin group (group S). Lipopolysaccharide (LPS) 3 mg/kg was intratracheally infused to prepare endotoxin-induced lung injury model in L and S groups, while the equal volume of normal saline was given instead in group C. Sitagliptin 100 mg/kg was intraperitoneally injected at 1 h before LPS infusion in group S, and normal saline was intraperitoneally injected at 1 h before endotracheal infusion in C and L groups. The arterial blood samples from femoral artery were taken at 24 h of LPS or normal saline infusion for measurement of PaO 2 and glucose levels.The mice were then sacrificed, and broncho-alveolar lavage fluid (BALF) and lung tissues were collected for determination of the concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)in serum and BALF (by enzyme-linked immunosorbent assay), wet/dry weight ratio (W/D ratio), expression of MUC5AC (by immunohistochemistry and immunohistochemical comprehensive score), and expression of MUC5AC mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and for examination of the pathological changes of lung tissues (using haematoxylin and eosin staining) which were scored. Results:Compared with group C, PaO 2 was significantly decreased, the glucose levels, W/D ratio and lung injury score were increased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were increased, and the expression of MUC5AC mRNA in lung tissues was up-regulated in L and S groups( P<0.05). Compared with group L, PaO 2 was significantly increased, the glucose levels, W/D ratio and lung injury score were decreased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were decreased, and the expression of MUC5AC mRNA in lung tissues was down-regulated in group S( P<0.05). Conclusions:The mechanism by which sitagliptin alleviates endotoxin-induced lung injury is related to down-regulation of MUC5AC expression in mice.

OBJECTIVE: To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism. METHODS: Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney. RESULTS: Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney. CONCLUSION Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.
Albuminuria ; Animals ; Blood Glucose ; Collagen Type IV ; metabolism ; Curcumin ; pharmacology ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; drug therapy ; Female ; Fibronectins ; metabolism ; I-kappa B Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; Mice ; Phosphorylation ; Proteinuria ; STAT3 Transcription Factor ; metabolism