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 summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.

Objective:To study the relationship between white matter injury (WMI) and brain maturity in preterm infants at full-term corrected gestational age (cGA).Methods:A retrospective study was performed in preterm infants [GA≤32 weeks or birth weight (BW) ≤1 500 g] admitted to the neonatal intensive care unit of the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to August 2018 and the Northwest Women and Children's Hospital from January 2017 to June 2017. The infants received conventional magnetic resonance imaging (MRI) at cGA 37~42 weeks. The infants were assigned into the WMI group and the control group according to the WMI scoring system, including the total maturation scores (TMS) and four sub-item scores.Results:A total of 118 premature infants were enrolled in this study (17 cases in the WMI group and 101 cases in the control group). The GA was (30.3±1.7) weeks, and BW was (1 356±268) g. The proportion of delayed TMS in the WMI group was significantly higher than the control group [58.8%(10/17) vs. 31.7%(32/101), P<0.05]. The TMS of the WMI group were significantly lower than the control group [(10.7±1.8) vs. (11.8±1.5), P<0.05]. The sub-item scores of TMS showed that the myelination [(2.8±0.6) vs. (3.1±0.4), P<0.05] and glial cell migration bands of the WMI group [(1.6±0.4) vs. (2.1±0.6), P=0.004] were significantly lower than the control group and no significant differences existed in cortical folding and involution of germinal matrix tissue scores between the two groups. Conclusions:The brain maturity of preterm infants with WMI is substantially delayed than those without WMI, including delayed myelination and delayed disappearance of glial cell migration bands.

Objective To investigate the prognostic factors of patients with upper urinary tract urothelial carcinoma (UTUC) treated with gemcitabine plus cisplatin (GC).Methods The clinical and follow-up data of 80 patients with UTUC admitted to Beijing Friendship Hospital,Capital Medical University from January 2013 to July 2018 were retrospectively analyzed.All patients underwent UTUC radical surgery.All patients were treated with GC regimen:1,8,and 15 days,Gemcitabine 800 mg/m2,intravenous infusion over 30 min;day 2 Cisplatin 70 mg/m2,protected from light 2 h intravenous drip;28 d for 1 cycle.Adjuvant treatments such as acid suppression,hydration,and antiemetic were given before and after chemotherapy.Patients completed 1 to 5 cycles with an average of 2 cycles.The patient's age,gender,presence or absence of water,primary tumor site,tumor stage and grade,lymphatic vascular infiltration,tumor recurrence,lymph node metastasis,organ metastasis,chemotherapy cycle,total Survival,etc.are used as indicators ofobservation.Univariate analysis of the patient's overall survival,screening for clinical variables associated with prognosis,and then using the COX proportional hazards model for multivariate prognostic analysis to determine independent influencing factors.Results Eighty patients with UTUC were followed up for 2 to 72 months with a median follow-up of 27 months.Sixteen patients (20％) died of UTUC recurrence or metastasis,and 64 (80％) patients survived.The 1-year cumulative survival rate was 78.26％ (18/23),and the 2-year cumulative survival rate was 54.18％ (9/13 ×78.26％),the 3-year cumulative survival rate was 39.41％ (8/1 1 × 54.18％),the 4-year cumulative survival rate was 31.53％ (12/15 × 39.41％),and the 5-year cumulative survival rate was 28.66％ (10/11 × 31.53％).Univariate analysis showed combined hydronephrosis (P =0.023),lymphatic vessel infiltration (LVI) (P =0.001),tumor TNM stage (P =0.002),tumor recurrence (P =0.008),simple lymph node metastasis (P =0.005),organ metastasis (P ＜ 0.001) was related to survival rate.COX model multivariate analysis showed that the independent risk factors associated with survival of patients with UTUC receiving chemotherapy with GC regimen were hydronephrosis (HR =4.355,95％CI:1.232-15.390,P=0.022),LVI (HR =0.133,95％ CI:0.035-0.509,P=0.003),TNM stage (HR=0.099,95％CI:0.010-0.929,P=0.043).Conclusion The presence or absence of hydronephrosis,LVI,and tumor TNM staging are independent factors influencing the prognosis of patients with UTUC who have adjuvant chemotherapy.