Objective:By sorting out the occurrence of the risk outcomes of scientific research project in the hospital, conducting root-cause analysis, the risk management theory, process and methodologies are introduced into the management system of hospital scientific research projects to reduce the occurrence of risk outcome of scientific research projects.Methods:Through literature review and the reflection of daily scientific research management practice, the risk characteristics of clinical scientific research projects were systematically summarized, comparative analysis were conducted to explore the effectiveness before and after the introduction of risk management, and the practical experiences of scientific research project risk management were summarized.Results:There are mainly six types of internal and external risks in hospital scientific research projects, which lead to project termination, project modifications, project delays, assessment index adjustments, budget adjustments and other risk issues. By establishing scientific research project risk management environment, standardizing risk management procedures, as well as establishing risk-monitoring and early warning information system, the introduction of risk management system enables more effective control of scientific research project risks in hospitals.Conclusions:The application of risk management in the management of scientific research projects in hospitals has showed positive impact. The risk management of scientific research projects in hospitals has certain practical value and feasibility. The exploration of risk management theories and methods should be continued to promote the high-quality development of hospital scientific research project management.

Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

Objective:To detect the expression of microRNA-218 (miR-218) in human acute lymphocyte leukemia (ALL) T lymphocytes ( CCRF-CEM) ,explore its effects on the biological features of CCRF-CEM cells and the expression of its target gene c-kit, so as to provide new insights for leukemia treatment.Methods: Using the quantitative real-time polymerase chain reaction ( qRT-PCR) ,we detected the expression of miR-218 in the normal peripheral blood T lymphocytes and CCRF-CEM cells.Forty-eight hours after the miR-218 mimic was transfected into the CCRF-CEM cells,the expression of miR-218 in the CCRF-CEM cells was detected by qRT-PCR.The effect of miR-218 on the CCRF-CEM cell viability was detected using MTT.The effect of miR-218 on the proliferation and apoptosis of CCRF-CEM cell was analyzed using flow cytometry.c-kit gene was identified to be a target gene of miR-218 by luciferase reporter enzyme system,and the effect of miR-218 on the expression of KIT protein in cells were determined using Western blot.Results:As shown by qRT-PCR,compared with that in the normal peripheral blood T lymphocytes,the expressions of miR-218 in ALL T lymphocytes cell lines were significantly decreased ( P<0.01 ) .Compared with the control group, the expression of miR-218 increase significantly in CCRF-CEM cells transfected with miR-218 mimic for 48 hours ( P<0.01).MTT showed that the cell viability decreased significantly after the over-expression of miR-218 in the CCRF-CEM cells ( P<0.05 ) .Flow cytometry showed that the S-phase fraction significantly declined after the over-expression of miR-218 ( P<0.01 ) , and meanwhile the apoptosis of cells also significantly increased (P<0.01).Luciferase reporter gene assay showed that,compared with the control group,the relative luciferase activity significantly declined in the miR-218 mimic transfection group (P<0.01).Compared with the control group,the expression of KIT protein in the CCRF-CEM cells transfected with miR-218 mimic for 48 hours significantly decreased ( P<0.01).Conclusion:The expression of miR-218 decreases in ALL T lymphocytes cell lines.MiR-218 can negatively regulate the expression of KIT protein,inhibit the proliferation and increase the apoptosis of CCRF-CEM cells.Treatment based on the enhanced expression of miR-218 may be a promising strategy for leukemia.

Background and objectivehTe prognosis for patients with lung cancer and brain metastases remains poor, with approximately 6 months of survival, despite active measures atfer treatment. In this study, we determined and ana-lyzed clinical parameters that affect the survival of patients with lung cancer and brain metastases to provide clinical guidance. MethodsLung cancer cases with brain metastases were retrospectively collected during 2002 and 2008 from Shanghai Chest Hospital, Shanghai Jiao Tong University.Kaplan-Meier method andCox regression were performed for univariate and multi-variate analyses, respectively, to explore independent predictors inlfuencing the survival of patients with lung cancer and brain metastases.Results Age, Eastern Cooperative Oncology Group performance status (ECOG PS), metastasis interval, number of metastasis, treatment method, treatment period, symptoms of brain metastases, extracranial metastasis, and brain metastasis order were factors that affect the survival of patients with brain metastases as conifrmed through theKaplan-Meiermethod. Treatment periods and extracranial metastasis were independent survival predictors in patients with lung cancer and brain me-tastasis as indicated byCox proportional hazard model.ConclusionTreatment periods and extracranial metastasis were inde-pendent predictors of survival of patients with lung cancer and brain metastasis. Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis.

Background and purpose:The effective rate of ifrst-line chemotherapy for advanced lung cancer is 30%-40%. The purpose of this study was to evaluate the efifcacy and adverse effects of pemetrexed combined with carboplatin or cisplatin in the treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods:One hundrend and twenty-one patients with advanced non-squamous NSCLC were enrolled in this study and all of these patients had been conifrmed with pathology or cytology. Among the 121 cases, 60 cases were male and 61 were female, the median age was 59 years, adnenocarcinoma in 113 patients and large cell carcinoma in 8 patients. Combination regimen: patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 or cisplatin 70 mg/m2 on day 1 by intravenous infusion, administrated every 3 weeks for 2 to 6 cycles. All patients who received 2 or more cycles could be evaluated. Disease control rate (DCR) was the primary end point; secondary end points included progression-free survival (PFS), 1-year survival rate and safety.Results:There was 1 case with complete response (CR), 44 cases achieved partial response (PR), 50 had stable disease (SD) and 26 cases had progressive disease (PD) in the overall cases. ORR and DCR were 37.2% (45/121) and 78.5% (95/121), respectively. The median PFS time was 5.2 months and 1-year survival rate was 59.0%. In pemetrexed combined with carboplatin group, the ORR and DCRwere 38.3% (23/60) and 78.3% (47/60), respectively; The median PFS was 5.1 months (95%CI: 3.8-6.4 month) and 1-year survival rate was 55.2%. The patients treated with pemetrexed plus cisplatin, the ORR and DCR were 36.1% (22/61) and 78.7% (48/61), respectively. Median PFS was 6.2 months (95%CI: 4.3-8.1 month) and 1-year survival rate was 62.5%. There were no statistical differences between carboplatin/pemetrexed and cisplatin/pemetrexed for both ORR, DCR, PFS and 1-year survival rate (P>0.05). The major adverse effects were leukopenia, neutropenia, fatigue and gastrointestinal reaction.Conclusion:Pemetrexed plus platinum chemotherapy could be considered as the ifrst-line treatment option for advanced non-squamous NSCLC patients. Pemetrexed combined with carboplatin/ cisplatin regimen has efifcacy with mild toxicity and better tolerability.

10.3969/j.issn.1007-3969.2013.05.002

Background and objective 50%-70%of patients with advanced lung cancer will develop bone metas-tases. hTe aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods iftfy BALB/C-nu/nu nude mice were grouped into ifve groups on average randomly. Cells of the four cell lines were injected into the letf cardiac ventricle of mice in the four experimental groups (0.2 mL/mouse) respectively;meanwhile, mice in the control group were injected with normal saline (0.2 mL/mouse) in the same manner. Periodical radio-logical examination was carried out to supervise the variation of the mice since the second week atfer injection. When mice in each group became thin obviously, end the experiment of this group. Before the end, pathological sections of bone tissues were made. We classiifed the bone metastatic sites into axial skeleton and limb bone, in order to compare the metastatic rates of these two different parts. hTe bone metastatic abilities of the four cell lines was statistically analyzed by comparing the average time cost in the appearance of bone metastases and the percentage of bone metastases among the experimental groups. Results Different metastatic sites which had been identiifed both by MicroCT and pathological sections appeared in each group of the four experimental groups. By contrast, no metastasis was observed in the control group. hTe percentage of cancer metastasiz-ing to axial skeleton was remarkably higher than the percentage of tumor metastasizing to the limb bone in each experimental group, which was consistent with the clinical regularity and characteristics of skeletal metastases with lung cancer. hTus, the model has been established triumphantly. However, there were no statistical differences in the average time consumed and skeletal metastatic rate among the four experimental groups. Conclusion hTe disruption in the bone can be clearly detected by MicroCT, which is beneift to supervise the osseous metastasis. We successfully developed the nude mice bone metastasis model of lung adenocarcinoma, which will pave the way for exploring novel prevention and therapy strategies clinically. hTe four cell lines varied in invasion and migration abilities in vitro, but there was no statistical difference in the metastatic ability in vivo, and the reason need to be explored further in future.

Objective To study the effect of ratanasampil (RNSP) which is Traditional Tibetan Medicine on the levels of serum β-amyloid protein, interleukin and tumor necrosis factor alpha (TNF-α) in patients with mild to moderate Alzheimer's disease (AD). Methods One hundred AD patients were divided into two groups in randomized controlled study, including treatment group (RNSP 1 g/d) and control group (piracetam 2.4 g/d). The treatment lasted 12 weeks. The Mini Mental State Examination (MMSE), Alzheimer' s disease Assessment Scale-cognitive subscale (ADAS-cog) and Activity of Daily Living Scale (ADLs) were taken to evaluate the efficacy. Serum levels of amyloid peptides (Aβ40 and Aβ42 ) were measured by ELISA assay. The radioimmunologic assay was used to determine the serum levels of IL-1β, IL-2, IL-6, IL-8 and TNF-α. Results The scores of MMSE, ADAS-cog and ADL significantly improved at 12 weeks after RNSP treatment (P＜0.01, 0.01, 0.05, respectively), while had no significant changes in piracetam group (P＜0.05).The levels of TNF-α, IL-1β, IL-6 and Aβ42 were significantly lower in RNSP group than in Piracetam group (P＜0.01). There was a decrease trend of the Aβ42/Aβ40 ratio at 12 weeks after RNSP treatment (P＜0. 05, P＜0.01 ). The serum Aβ42 level had strong correlations with TNF-α, IL-1 β and IL-6. There were no significant differences in Aβ40 and IL-8 between RNSP group and piracetam group. No obvious drug side effect happened on the groups. Conclusions The reductions of serum TNF-α, IL-1β and IL-6 levels after RNSP treatment may lead to decrease of Aβ42 production in AD patients. RNSP may decrease the Aβ42/Aβ40 ratio and slow down the progress of AD. It may improve the learning and memory ability in treating patients with mild to moderate AD and is well tolerated and safe.

BACKGROUND AND OBJECTIVEThe aim of this study is to evaluate diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis ofbronchogenic carcinoma.

METHODSBetween July, 2009 and February, 2010, 95 patients with mediastinal/hilar lymphadenopathy and/or intrathoracic peritracheal or peribronchial masses previously detected with CT scan underwent EBUS-TBNA. No rapid onsite cytology was performed.

RESULTSIn all 95 patients, 60 cases were newly diagnosed lung cancer through the pathological examination and clinical follow-up certification. In 60 lung cancer cases, 112 samples were obtained from lymph nodes (LNs) and 11 samples were obtained from intrapulmonary lesions. Fifty-eight cases of patients were diagnosed, false negative in 2 cases. Sensitivity and specificity of EBUS-guided TBNA method in distinguishing benign from malignant LNs or thoracic masses were 96.67% and 100%, respectively. There was any major complication in this series, the procedure was uneventful.

CONCLUSIONEBUSTBNA seemed a safe and effective technique in making bronchogenic carcinoma diagnosis for mediastinal/hilar LNs and intra-pulmonary masses.

Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; methods ; Bronchi ; diagnostic imaging ; pathology ; Carcinoma, Bronchogenic ; diagnosis ; Endosonography ; methods ; Female ; Humans ; Lung Neoplasms ; diagnosis ; Male ; Middle Aged

Background and purpose:Both very important therapeutic targets of NSCLC,vascular endothelial growth factor (VEGF) and epidermal growth factor receptors (EGFR),are over expressed in non-small cell lung cancer (NSCLC).The aim of this study was to discuss the expression of VEGF and EGFR in NSCLC as well as its clinical significance.Methods:The expression of VEGF and EGFR was detected in 186 NSCLC samples using the immunohistochemical method.The expression of VEGF and VEGR in NSCLC patients with various pathological characteristics was observed and the correlation between them was analyzed.Results:The expression of VEGF in NSCLC was correlated with lymph node metastasis (P