Purpose To investigate the corr-elation between Rap1 GAP expression in colon cancer tissues and clinicopatho-logical features and prognosis.Methods Immunohistochemistry was used to detect Rap1 GAP protein expression in 125 cases of colon cancer,and its correlation with clinicopathological features and prognosis was analyzed.Rap1 GAP protein expression in co-lon cancer LOVO,HCT116,SW480 cells and normal colon epi-thelial HCoEPiC cells was detected by Western blot.The expres-sion of Rap1 GAP was down-regulated and up-regulated in LO-VO,HCT116 and SW480 cells by lentivirus transfection,and di-vided into no-load group(sh-NON,LV-NON),sh-Rap1 GAP group(low expression Rap1 GAP)and LV-Rap1 GAP group(overexpression Rap1 GAP)according to different treatments.The transfection efficiency was verified by Western blotting.MTT assay and Transwell assay were used to detect cell proliferation,invasion and migration in each group.Results In 125 colon cancer samples,83 cases(66.4％)had the loss of Rap1 GAP expression,which was higher than that in paracancer control(7.2％,P＜0.001).The rate of loss of Rap1 GAP expression was correlated with the degree of tumor differentiation(x2=6.152,P=0.011)and the presence of mucinous adenocarcino-ma(x2=4.908,P=0.028),but not with gender,age,tumor location,tumor stage,or lymph node metastasis(P＞0.05).Western blotting results showed that compared with HCoEPiC(0.189±0.081)cells,Rap1 GAP protein expression was in-creased in colon cancer LOVO(0.238±0.008)cells.Rap1 GAP protein expression was decreased in HCT116(0.064± 0.002)and SW480(0.152±0.026)cells(F=159.6,P＜0.05).After LOVO cells were transfected with Rap1 GAP low expression lentivirus,the expression level of Rap1 GAP in sh-Rap1 GAP-1 group(0.733±0.071)and sh-Rap1 GAP-2 group(0.559±0.136)and sh-Rap1 GAP-3 group(0.606±0.037)was significantly lower than that in LOVO group(1.880± 0.129)(F=49.57,P＜0.05).Compared with sh-NON(1.260±0.109)group,the proliferation ability of sh-Rap1 GAP-2(1.569±0.059)and sh-Rap1 GAP-3(1.548±0.087)cells was significantly increased at 72 h(F=28.36,P＜0.05).Its invasion and migration ability were significantly increased(P＜0.05).After HCT116 cells transfected with overexpression lentivirus,the expression of Rap1 GAP protein in LV-Rap1 GAP group(1.395±0.137)was relatively higher than that in LV-NON group(0.485±0.097)(P＜0.05).The results of MTT assay showed that compared with LV-NON(0.652±0.047)group,the proliferation ability of cells in LV-Rap1 GAP(1.212 ±0.038)group was decreased,and the invasion and migration ability were significantly decreased(P＜0.05).The transfection results,proliferation,invasion and migration of SW480 cells were consistent with those of HCT116 cells.Conclusion The loss rate of Rap1 GAP expression is related to the differentiation degree of colon cancer and whether it is accompanied by mucin-ous adenocarcinoma.The up-regulation of Rap1 GAP expression can inhibit the proliferation,invasion and migration of colon cancer cells,providing a theoretical basis for exploring the occur-rence and development of colon cancer.

Objective:To construct a prediction model for ventilator-associated pneumonia (VAP) in mechanically ventilated preterm infants in the neonatal intensive care unit (NICU) and to test its clinical effect.Methods:This was a cross-sectional study. A total of 740 preterm infants admitted to the NICU for mechanical ventilation from July 2018 to June 2023 were retrospectively selected as the study subjects, and were divided into the modeling set (518 cases) and the validation set (222 cases) according to the ratio of 7∶3 using the computer-generated random number method. The modeling set was divided into the VAP group (181 cases) and the non-VAP group (337 cases) according to whether VAP occured, and 21 clinical characteristics were analyzed, using single factor difference analysis to screen predictive factors, the independent risk factors of VAP in mechanically ventilated preterm infants were determined by multivariate Logistic regression analysis, and the nomogram model was made by R software. Then, the nomogram model was tested by validating the data of the validation set. The receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test, calibration curve and clinical decision curve were used to evaluate the efficacy and practical value of the model.Results:There were 88 males and 93 females in the VAP group, with 156 cases of gestational age<34 weeks and 25 cases of gestational age≥34 weeks. There were 155 males and 182 females in the non-VAP group, with 196 cases of gestational age<34 weeks and 141 cases of gestational age≥34 weeks. Birth weight ( OR=0.114, 95% CI 0.044-0.268, P<0.05) and oral care of breast milk ( OR=0.124, 95% CI 0.0.057-0.249, P<0.05) were protective factors for VAP in mechanically ventilated preterm infants, and Apgar score at 5 min after birth ( OR=2.895, 95% CI 1.318-6.419, P<0.05), serum prealbumin at 72 h of mechanical ventilation ( OR=4.837, 95% CI 2.643-9.063, P<0.05), gastric contents reflux ( OR=6.754, 95% CI 3.156-15.240, P<0.05), and time of mechanical ventilation ( OR=7.784, 95% CI 3.491-18.160, P<0.05) were independent risk factors for VAP in mechanically ventilated preterm infants. The area under the curve (AUC) of the ROC curve of the modeling set was 0.929 (95% CI 0.907-0.950, P<0.01), and the validation set (AUC) was 0.917 (95% CI 0.882-0.952, P<0.01), the model has good discrimination. The C indices of the modeling set and the validation set were 0.93 and 0.92 respectively by sampling 500 times by the Bootstrap method, indicating that the model had good consistency, and the decision curve suggested that the prediction model was far from the extreme curve and the net return value was high, indicating that the nomogram prediction model constructed this time had high prediction value. Conclusions:Birth weight, Apgar score at 5 min after birth, time of mechanical ventilation, oral care of breast milk, serum prealbumin at 72 h of mechanical ventilation, and gastric contents reflux are independent influencing factors for VAP in mechanically ventilated preterm infants. The nomogram prediction model constructed can provide a visual and simple evaluation tool for early identification of high-risk children and reducing the occurrence of VAP.

Objective:To evaluate the feasibility and clinical value of pre-treatment non-enhanced chest CT radiomics features and machine learning algorithm to predict the mutation status and subtype (19Del/21L858R) of epidermal growth factor receptor (EGFR) for patients with non-small cell lung cancer (NSCLC).Methods:This retrospective study enrolled 280 NSCLC patients from first and second affiliated hospital of University of South China who were confirmed by biopsy pathology, gene examination, and have pre-treatment non-enhanced CT scans. There are 136 patients were confirmed EGFR mutation. Primary lung gross tumor volume was contoured by two experienced radiologists and oncologists, and 851 radiomics features were subsequently extracted. Then, spearman correlation analysis and RELIEFF algorithm were used to screen predictive features. The two hospitals were training and validation cohort, respectively. Clinical-radiomics model was constructed using selected radiomics and clinical features, and compared with models built by radiomics features or clinical features respectively. In this study, machine learning models were established using support vector machine (SVM) and a sequential modeling procedure to predict the mutation status and subtype of EGFR. The area under receiver operating curve (AUC-ROC) was employed to evaluate the performances of established models.Results:After feature selection, 21 radiomics features were found to be efffective in predicting EGFR mutation status and subtype and were used to establish radiomics models. Three types models were established, including clinical model, radiomics model, and clinical-radiomics model. The clinical-radiomics model showed the best predictive efficacy, AUCs of predicting EGFR mutation status for training dataset and validation dataset were 0.956 (95% CI: 0.952-1.000) and 0.961 (95% CI: 0.924-0.998), respectively. The AUCs of predicting 19Del/L858R mutation subtype for training dataset and validation dataset were 0.926 (95% CI: 0.893-0.959), 0.938 (95% CI: 0.876-1.000), respectively. Conclusions:The constructed sequential models based on integration of CT radiomics, clinical features and machine learning can accurately predict the mutation status and subtype of EGFR.

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Antineoplastic Agents/therapeutic use* ; China ; Drug Industry ; Humans ; Lung Neoplasms/drug therapy* ; Pharmaceutical Preparations

Antitubercular Agents/therapeutic use* ; Axilla ; Humans

Objective:To investigate the relationship between metabolic syndrome (MetS) and clinicopathological characteristics of patients with gastric cancer.Methods:The clinicopathological data of 245 patients with gastric cancer diagnosed by pathology in Xinzhou People's Hospital of Shanxi Province from January 2015 to December 2018 were retrospectively analyzed, and 462 non-tumor patients who underwent routine physical examination at Xinzhou People's Hospital of Shanxi Province during the same period were selected as control group. The occurrence of MetS and the correlation of MetS with clinicopathological characteristics and overall survival of patients with gastric cancer were analyzed.Results:The incidence rate of MetS in 245 patients with gastric cancer was 21.6% (53/245) and 13.6% (63/462) in the control group, and the difference between the two was statistically significant ( χ2 = 7.464, P = 0.008). Among patients with gastric cancer, the incidence of postoperative lung infection in the MetS group and non-MetS group was 17.0% (9/245) and 3.1% (6/462), respectively, and the difference was statistically significant ( χ2 = 13.874, P = 0.001); there was no significant difference in the tumor site and the incidence of incision infection, abdominal cavity infection, anastomotic leakage, gastric emptying disorder, and overall survival between the two groups (all P > 0.05). In patients with gastric cancer, MetS was associated with poor histological differentiation and late TNM stage ( χ2 = 4.242, P = 0.040; χ2 = 5.547, P = 0.027). Conclusions:The incidence of MetS in patients with gastric cancer is higher than that in the general population, and MetS-related abnormalities are more common in patients with low differentiated, undifferentiated and advanced gastric cancer. MetS may play a role in the occurrence and development of gastric cancer.

Objective Based on the data of scientific research output in a top three hospital in Beijing from 2015 and 2016,stochastic frontier analysis is conducted to estimate the efficiency of scientific research performance in different departments of this hospital,so as to draw the impetus for the growth of departments.Methods According to the results of the stochastic frontier model,comprehensive analysis and evaluation are conducted for the research performance of various departments.Results The overall average technical efficiency of the hospital is 0.44,and improvement space for the technical efficiency of scientific research performance is still 0.56.There are significant differences in the technical efficiency of each department.Among the four major categories,the D section is higher than the technical efficiency of class A,B and C departments.Conclusions The overall technical efficiency of the hospital is not high,the level of scientific research output of the four types of departments is not balanced,which should be emphasized in the improvement of scientific research performance level.

Objective To study the dynamic changes of scientific research efficiency of 51 departments in a top three hospitals in Beijing from 2014 to 2016,and to provide reference information for improving the efficiency of scientific research in hospital departments.Methods The CCC model of DEA,BCC model were used for lateral analysis,and then Malmquist index was used for longitudinal analysis.Results There were 12 (23.53％) departments in 2014,11 (21.57％) departments in 2015,9 (17.65％) departments in 2016 data envelopment analysis was valid,from 2014 to 2016,41 (80.39％) departments of the hospital increased the total factor productivity.Conclusions The total factor productivity of the 51 departments in the hospital increased from 2014 to 2016,and technological progress was the main reason for its growth.

Objective Based on the three years' peer review data of a project fund,the results of fund peer review were analyzed and evaluated,to provide references for further improvement of the peer review and management.Methods Based on the fund's peer review results of 2145 projects in three years,descriptive statistics,single-item identification index were adopted,as well as RJ normality test,t-test and other statistical methods,to analyze and assess the overall data of fund,project categories,individual scores,etc.Results The score distribution of the three year peer review project of the fund is almost normal distribution,and the overall consistency of peer review shows a better trend.The analysis shows that the peer review experts of the fund have better consistency in terms of project innovation,rationality and characteristics.While there were differences in the peer review of applicability.Conclusions The three year peer review data of the fund show that three years' evaluation results are reliable,reasonable,and the quality of evaluation is good,showing a better development trend in both project quality and expert consistency.

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.