Risk model of breast cancer prognosis based on the expression profile of long non-coding RNA / 中国综合临床

Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.

Analysis and strategy research on the simulation teaching of airway management in teaching hospitals in China / 中华医学教育探索杂志

With the development of science and technology,medical simulation has been applied extensively.The application of simulation technique in teaching hospitals has become a new choice in modern medical education.As the most basic and important clinical ability,airway management has become a popular training program in China's teaching hospitals.This paper summarizes the current situation of the simulation training of airway management in teaching hospitals at home and abroad,concludesthe existing problems in the simulation teaching of airway management of teaching hospitals in China,such as narrow range of training objects,lack of professional teaching staff,unscientific curriculum design and outdated training model,etc.Then puts forward the countermeasures of expanding the training coverage,establishing the professional teaching team,designing the curriculum design of science,and introducing advanced simulation equipment to improve the quality of simulated teaching.

Effects of MTA1 on biological behaviors of gastric cancer cells / 中华肿瘤杂志

Objective@#To study the effects of metastasis associated 1 (MTA1) on biological characteristics such as migration, invasion and proliferation of gastric cancer (GC) cells.@*Methods@#pSilencer3.1-MTA1-siRNA vector was used to establish human gastric cancer BGC-823 cell lines with constitutive MTA1-knockdown. Boyden, wound healing, clony forming assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay were performed to identify the effects of MTA1-deficiency on the biological behaviors of BGC-823 cells in vitro. Simultaneously, MTA1 overexpressed BGC-823 cell line was established by pcDNA3-MTA1 plasmid transfection for reverse verification. In addition, the role of MTA1 in the tumorigenicity of gastric cancer BGC823 cells in vivo was examined by subcutaneous injection of BGC-823 cells expressing different MTA1 levels into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the expression levels of integrin β1, cyclin D1 and uPAR in pSilencer3.1-MTA1-siRNA, pcDNA3-MTA1 transfected cells and control cells.@*Results@#MTA1 knocked down or upregulated BGC-823 cell lines were successfully generated by transfecting pSilencer3.1-MTA1-siRNA or pcDNA3-MTA1 vector with lipofectamine 2000, respectively. The Boyden and wound healing experiments showed metastasis and invasion ability in MTA1 knocked down cells (25±2, 12±1) were significantly decreased when compared with those of control (78±2, 50±2) and MTA1-overexpressed groups (218±2, 269±3; P<0.05). The results of MTT assay and colony forming assay were significantly decreased when compared with those of showed that MTA1 overexpressed cells grew more rapidly and formed more colonies in vitro and induced worse malignant tumors in vivo, while MTA1 knocked down cells presented the reversed phenotype[control group (1 482.41±511.90) mm3, (1.39±0.29)g; MTA1 overexpressed group [(3 158.73±1 823.22) mm3, (2.23±0.51)g; MTA1-downregulated group (711.32±284.30)mm3, (0.87±0.21) g ; P<0.05)]. In addition, RT-PCR result showed that the expression level of MTA1 was positively correlated with the known metastasis-related genes (integrinβ1, cyclinD1, uPAR).@*Conclusions@#MTA1 promotes the invasion, migration and proliferation of human gastric cancer BGC-823 cells. On the contrary, down-regulation of MTA1 significantly inhibits tumorigenicity of BGC-823 cells and induces favorable phenotypes. MTA1 may promote the malignant phenotype of BGC-23 cells via regulating the expressions of integrinβ1, cyclinD1 and uPAR.

Effects of esophageal cancer cell-derived exosomes on cancer cell migration and invasion and its mechanism research / 解放军医学杂志

Objective To investigate the biological effects of exosomes secreted by KYSE410 cells on migration and invasion of KYSE410,KYSE510,YES2 cells and the possible mechanisms underlying the phenotype change.Methods The exosomes were isolated from the conditional supernatant of esophageal cancer cell line KYSE410 by ultracentrifugation.The morphology of exosomes was observed by transmission electron microscopy (TEM).Western blotting was used to detect the protein markers of exosomes.The uptaken of fluorescence-labeled KYSE410 exosomes by KYSE410,KYSE510 and YES2 was also recorded under confocal microscopy.Migration and invasion ability of the three esophageal carcinoma cell lines and the effects of exosomes from KYSE410 on migration and invasion of KYSE410,KYSE510 and YES2 cells were analyzed by Transwell chamber,respectively.The alteration of Wnt/β-catenin and PI3K/Akt pathway-related proteins were detected by Western blotting.Results The membrane structure of KYSE410 derived exosomes could be observed with its diameter ranged between 30-100nm.The invasion and migration ability of three esophageal cancer cells are KYSE410＞ KYSE510＞ YES2.KYSE410 exosomes promoted the migration and invasion of KYSE410,KYSE510 and YES2 cells.Conclusions Concentrated exosomes derived from the highly migratory and invasive esophageal cancer cell line KYSE410 promoted the migration and invasion potentials of itself and esophageal cancer cell lines KYSE510 and YES2,which possibly exerted the effects by activating Wnt/β-catenin and PI3K/Akt signaling pathways.

Random Forests algoritm-based bioinformatic screening of functional genes involved in lymph metastasis of cervical cancer / 中国生化药物杂志

Objective To screen the genes most relevant to lymph node metastasis of cervical cancer and identify the genes at the key knots of the regulatory network to provide the potential targets for cervical cancer intervention.Methods The transcriptional profiling database of TCGA was used, and random forests algorithm was adopted to rank the genes related to lymph node metastasis extracted from GeneCards database.STRING and Cytospace tolls were used to build the interactive regulatory network and identify the most weighted genes localized in the central of the network.DAVID platform was used to perform a functional annotation for the whole geneset.Results We ranked 2784 genes in respect to their potential contributions to lymph node metastasis of cervical cancer and identified the genes at the key knob.The genes related to cancer metastasis were enriched to cytokines pathway, MAPK pathway, wnt pathway, intercellular interaction, adhesive conjunction, cellular skeleton regulation, etc.Some of the identified key genes, like EGFR, NOTCH1, RHOA, etc. have been verified to be closely related cervical cancer metastasis in the basic and clinical research. Conclusion Random forests algorithm is useful, taking advantages of TCGA database, in enriching the genes playing significant role in cervical cancer metastasis.A majority of the genes in the analyzed geneset were indicated to be significantly correlated with lymph node metastasis.

The effect of tumor metastasis associated gene 1 on the process of epithelial-mesenchymal transition in esophageal squamous cell carcinoma / 中国综合临床

Objective To explore the effect and mechanism of metastasis associated gene 1 (MTA1) on epithelial-mesenchymal transition(EMT) of esophageal squamous cell carcinoma(ESCC).Methods Lentivirus infection method was used to establish the MTA1 knocking out cell line (LV3-shMTA1-KYSE410) and the MTA1 overexpressing cell line (LVS-MTA1-KYSE450).Western Blot was used to measure the expression of MTA1 and the proteins associated with EMT process.Furthermore,the expression and localization of E-cadherin and Vimentin were observed by immunofluorescence assay under confocal microscope.Finally,the wound healing method was performed to confirm the changes of migration ability of the established cell lines.Results When KYSE-450 cells were overexpressed MTA1,the expression level of E-cadherin was down-regulated while Vimentin was up-regulated,and the migration ability was enhanced (0.91 ± 0.00 vs.0.23 ± 0.04,P ＜0.05).When MTA1 was knocked out in KYSE-410 cells,the results were the opposite (0.19±0.01 vs 0.53±0.01,P ＜0.05).Conclusion Overexpression of MTA1 may promote the process of epithelial-mesenchymal transition and enhance the migration ability of ESCC.

Practice and enlightenment of cardio-pulmonary resuscitation emergency training / 中华医学教育探索杂志

Objective Based on the international standard cardio-pulmonary resuscitation curriculum, the aim of the study is to investigate the effectiveness and importance of the layered cardio-pulmonary resuscitation emergency training. Method A total of 219 trainee including clinical medical personnel , auxiliary medical personnel and medical staff with standardized training were enrolled . Training included watching course video, team practice and class discussion, and the theoretical score and operation marks before and after layered cardio-pulmonary resuscitation training were compared. Theoretical score were compared by paired T-test, and operation pass ratio was determined byχ2 analy-sis. Results The pre- and post-training theoretical score of medical staff with standardized training, auxiliary medical personnel, and clinical medical personnel were 66.60±7.82 vs. 88.60±6.37;61.60± 7.44 vs. 86.90±5.80;73.45±6.83 vs. 94.75±5.04 respectively. The pre- and post-training operation pass ratio of marks of medical staff with standardized training, auxiliary medical personnel, and clinical medical personnel were 31.1%/85.2%;32.0%/90.7%;59.0%/96.4% respectively. Conclusion There are differences in both the theory and operation results of medical personnel at different levels before and after the training of cardiopulmonary resuscitation. The more targeted and layered training is much effective in cardio-pulmonary resuscitation emergency training.

The clinical value of atrial natriuretic peptide,endothelin-1 and von Willebrand factor in newborns with persistent pulmonary hypertension after the treatment of sildenafil / 中国医师进修杂志

Objective To study the changes and significance of plasma atrial natriuretic peptide (ANP),endothehn-1 (ET-1),von Willebrand factor (vWF) levels in newborns with persistent pulmonary hypertension (PPHN) after the treatment of sildenafil.Methods Sixty-six cases with PPHN group and 40 cases with non-PPHN (control group) were enrolled.PPHN group was in the treatment of sildenafil.Collected the blood when before the treatment of sildenafil and 3,7 d after treatment,respectively.Arterial blood gas were done and pulmonary arterial systolic pressure (PASP) was measured before treatment and 3,7 d after treatment,and by the same time recording pulse oxygen saturation (SpO2).Plasma ANP,ET-1,vWF levels were measured by ELISA method.Results The levels of PASP,SpO2 arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and plasma ANP,ET-1,vWF in PPHN group before treatment [(66.5 ± 13.4)mm Hg (1 mm Hg =0.133 kPa),0.726 ±0.531,(46.3 ±7.2)mm Hg,(59.2 ± 7.4) mm Hg,(272.6 ± 20.3)ng/L,(221.3 ± 24.3) ng/L,(142.5 ± 20.3)％] compared with controlgroup [(25.0±6.2) mm Hg,0.896 ± 0.767,(88.3 ±7.6) mm Hg,(41.1 ±6.1) mm Hg,(68.4 ± 7.9) ng/L,(39.8 ± 6.5) ng/L,(95.3 ± 18.5)％] were statistically significant(P ＜ 0.05).Their levels in PPHN group 3 dafter treatment[(48.3 ± 3.2) mm Hg,0.841 ± 0.416,(73.6 ± 9.3)mm Hg,(50.5 ± 7.2) mm Hg,(102.6 ±20.3) ng/L,(79.6 ± 15.2) ng/L,(103.6 ± 14.1)％] were significantly improved,there was significantdifference compared with before treatment and control group(P ＜ 0.05).Their levels in PPHN group 7 d aftertreatment [(25.2 ± 3.6) mm Hg,0.882 ± 0.724,(85.4 ± 7.4) mm Hg,(40.2 ± 6.4) mm Hg,(64.4 ± 3.6)ng/L,(37.3 ± 5.4)ng/L,(92.9 ± 11.7)％] were significantly improved,there was significant difference compared with 3 d after treatment (P ＜ 0.05),the difference was no statistically significant compared with control group (P＞ 0.05).Linear correlation analysis showed that ANP,ET-1,vWF and PASP,PaCO2 were significantly positively correlated (P ＜ 0.01),ANP,ET-1,vWF and SpO2,PaO2 were significantly negatively correlated (P＜ 0.01).On the basis of cardiac ultrasound monitoring PASP,ANP evaluation of the efficacy of sildenafil sensitivity was 82.2％,specificity was 83.4％ ;ET-1 was 86.4％ and 87.6％; vWF was 85.1％ and 84.7％.Conclusion ANP,ET-1,vWF may play an important role in the mechanism of the treatment of PPHN by sildenafil,and could be used as an objective index to evaluate the effect of sildenafil on PPHN.

Investigation and analysis of clinical skill training course / 中华医学教育探索杂志

Objective To improve the clinical skill training courses in order to meet the new challenges and different requirements. Methods Totally 327 clinical physicians of different levels in 36 departments were enrolled and 286 physicians were randomly surveyed with the questionnaire , including subjects' general characteristics, participation rate, training courses and training model. Results Among the trainees, most of them were attending physician and resident physician, and their participation rate was 88.5%(77/87) and 90.0% (172/191) respectively. The most popular and well acknowledged training courses were emergency treatment course such as AHA basic/advanced life support course. Training model like ‘group class, one topic, one hour’ was well accepted by 84.1%(275/324) physicians and course time of 16:30-17:30 was preferred by 65.5% (214/327) physicians. Conclusions A series of most popular and significant training courses are developed. More important-ly, physicians' real need and new expectation to the training course are well recognized, which is im-portant to plan the further training program and courses.

PUMA gene in cancer treatment / 国际肿瘤学杂志

PUMA (p53 up-regulated modulator of apoptosis) is a recently discovered Bcl-2 family member which could be rapidly induced by p53 and has strong pro-apoptotic effects.PUMA has attracted much attention in the research of life science.PUMA expression results in potent growth suppression of some cancer cells through induction of apoptosis.PUMA can also significantly sensitize some cancer cells to chemotherapeutic agents and irradiation through induction of apoptosis.PUMA is potentially useful in gene therapy of tumor.But recently,researchers have also found that PUMA participates in the process of carcinogenesis and possessed important biological functions.