Testing of hypothesis was affected by statistical analysis set division which was an important data management work before data base lock-in. Objective division of statistical analysis set under blinding was the guarantee of scientific trial conclusion. All the subjects having accepted at least once trial treatment after randomization should be concluded in safety set. Full analysis set should be close to the intention-to-treat as far as possible. Per protocol set division was the most difficult to control in blinded examination because of more subjectivity than the other two. The objectivity of statistical analysis set division must be guaranteed by the accurate raw data, the comprehensive data check and the scientific discussion, all of which were the strict requirement of data management. Proper division of statistical analysis set objectively and scientifically is an important approach to improve the data management quality.
Clinical Trials as Topic ; standards ; Databases, Factual ; Research Design ; standards ; Statistics as Topic

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.
Clinical Trials as Topic ; Data Collection ; methods ; standards ; Humans ; Models, Theoretical ; Research Design

Objective To investigate the relationship between the expression of ING4 and clinical primary breast cancer.Methods Tissue and peripheral blood samples of primary breast cancer patients were collected and the expression levels of ING4 and NF-κB in tissue samples were detected with immunohistochemistry.The expression of ING4 in the peripheral blood was detected with ELISA.Results The positive rates of expression of ING4 and NF-κB in breast cancer tissues were 100.00 ％ (30/30),which were significantly higher than that in the adjacent tissues 12.50 ％ (3/24) and 93.75 ％ (45/48) compared to 6.67 ％ (1/15) respectively.Compared with the preoperative,the ING4 level in peripheral blood from the postoperative breast cancer patients was significantly reduced (P =0.044).Conclusions The expression of ING4 does not decrease in the primary breast cancer patients.The increasing is perhaps due to the body's stress response against tumor development in early stage by secreting more ING4 protein.

R2) of the two models were 0.801,0.872 respectively. The fitting efficacy of the ARIMA-GRNN combination model was better than the single ARIMA, which had practical value in the research on time series data such as the incidence of scarlet fever.

Objective To investigate the expression of macrophage migration inhibition factor (MIF) and cell cycle regulating factor Cyclin D1 in hepatocellular carcinoma tissue and the interaction between MIF and Cyclin D1 in hepatocellular carcinoma cell cycle controlling. Methods Using quantitative real-time PCR and Western blotting to detect mRNA and protein expression of MIF and Cyelin DI in HCC tissues and tumor adjacent tissues. Specific small interfering RNA(siRNA) targeting MIF gene was transfccted at doses of 50 nmol/L and 100 nmoL/L into HCC cell lines of PLC and HepG2 with lipofeetamine 2000 methods to knockdown the expression of M1F gene and to investigare the the interaction between M1F and Cyclin D1. Results MIF and Cyclin D1 protein and mRNA were overexpressed in HCC tumor tissues. The relative expression of MIF,Cyclin D1 protein and mRNA were 0.825±0.13,0.843± 0.104 and 7.31±1.85 folds、4.27±1.05 folds, compared with the tumor adjacent tissues (FMIF= 15.5, P<0.01;FCyclin D1=87.5,P <0.01). In MIF siRNA treated PLC and HepG2 cells, MIF mRNA down regulation 71.2%±7.2%, 87.4%±2.9% ,74.3%±8.9% and 88.4%±4.6% respectively (FPLC = 315.5 ,P < 0.01 ; FHepG2= 201.2 P < 0.01). While MIF protein expression were significandy reduced to 0.33±0.03,0.11±0.02, 0.81±0.08 and 0.36±0.02 in a dose-dependent manner (FPLC= 43.9, P <0.01 ;FHepG2 = 133.4 P <0.01). Cyclin D1 mRNA was significantly down-regnlated in MIF siRNA treated PLC and HepG2 cell lines when compared with control group(P <0.01). In 50 nmol/L and 100 nmol/L groups, Cyclin DI mRNA levels were respectively decreased by 68.2%±3% and 78.1%±1.4% in PLC cell, 65.8%±4.7% and 77.3%±2.6% in HepG2 cell (FPLC= 1569, P < 0.01 ; FHepG2= 480.4, P <0.01). Compared with control groups, Cyclin D1 protein levels significantly reduced to 0.28±0.06、0.15±0.03 and 0.44 ±0.04、0.13±0.02 in the PLC and HepG2 after M IF siRNA treatment(FPLC= 35.5, P < 0.01 ; FHepG2 = 114.7, P < 0.01). Conclusions MIF and Cyclin D1 mRNA and protein were overexpressed in HCC tumor tissues and participated in tumor cell cycle regulation. MIF may up-regnlate the expression of Cyclin DI via ERK signalling and precipitate in carcinogenesis of hepatocellular carcinoma.

Objective To explore the feasibility and safety of the posterior approach of robotassisted laparoscopic radical prostatectomy and to the approach.Methods From November 2001 to April 2017,32 patients underwent posterior approach of robot-assisted laparoscopic radical prostatectomy.Patients aged 53 to 81 years,with mean of 66.9 years old.Their prostate volumes were 12.0-73.7 ml with an average of 32.9 ml.All patients were diagnosed by prostate biopsy before surgery.The operation time,blood loss and length of hospital stay were recorded.Results All the operations were completed by robotic assisted laparoscopy with no transition to open surgery.The surgery time was 129-210 minutes with an average of 163.6 minutes.The estimated blood loss was 20-200 ml with an average of 59.3 ml.The hospital stay was 8-21 days with an average of 12.8 days.The postoperative hospital stay was 3-13 days with an average of 6.9 days.The time of postoperative catheter removal was 4-14 days with an average of 7.5 days.Postoperative follow-up was 1-6 months.Twenty-four (75％) patients had early recovery of continence,and all (100％) patients regained continence 3-month postoperatively.Conclusion The posterior approach of robotic assisted laparoscopic radical prostatectomy was a safe and effective surgical technique,which was beneficial in early continence recovery.

Objective To explore the Electrocardiography (ECG) changes of residents in Keshan disease area and the status of growth and decline of Keshan disease in Shaanxi Province. Methods Using stratified randomized sampling method,2 mild,2 moderate and 2 serious disease counties were selected respectively in 2005 and 2006. A total of 6 counties were sampled,2 villages,one with severe disease and one with mild,were selected from each sampled county. A total of 12 villages were selected. The clinical examination and ECG were conducted in 3-year old children of agricultural population of the selected villages. Results ECG of 5692 cases were performed in the selected 12 village in the 6 counties,in which 4917 cases showed normal electrocardiogram,up to 86.38% (4917/5692). Two hundred and fifty-two cases showed roughly normal electrocardiograms,up to 4.43%(252/5692). Five hundred and twenty-three cases had abnormal electrocardiogram,accounting for 9.19% (523/5692). Among them,the abnormal electrocardiogram rates in mild,moderate and serious disease areas were 7.07% (144/2036), 11.41%(167/1646) and 10.54%(212/2010),respectively. Atrioventricular block was the major abnormal electrocardiogram change,followed by arrhythmia,ST-T changes,and low voltage. One hundred and thirty-nine cases were confirmed as latent and chronic Keshan diseases. One hundred and thirty-one cases were latent Keshan, and detection rate was 2.30%(131/5692). Eight cases were chronic Keshan,and the detective rate was 0.14% (8/5692). Complete right bundle branch block [37.06% (63/170) ],ST-T changes [22.35% (38/170) ],multiple premature ventricular beats [12.94% (22/170)] were the major abnormal electrocardiogram change of Keshan patients. Conclusions Atrioventricular block and arrhythmia are the major abnormal electrocardiogram changes. Keshan disease incidences are controlled under a stable condition.

Objective To know the prevalence tendency of Keshan disease(KSD) under control after 10 years in Shaanxi Province, the factors that causes or relative to the disease, to provide scientific reference for disease's prevention and control. Methods Through stratified cluster sampling, based on the severity of KSD in endemic area of Shaanxi Province, 12 villages from 6 counties were randomly selected as investigation points in 2006. The people older than 3 year-old were chosen to do clinical check up and electrocardiogram tracing. Among them, suspicious or abnormal cases were asked to take chest X-ray and cardiac ultrasound. Maize and rice, hair and whole blood were randomly collected to test the selenium content, the activity of Glutathione peroxidase (GSH-Px). Results The total detection rate of potential or chronic KSD was 2.44%(139/5694), the detection rate of abnormal ECG was 9.19% (523/5692), the detection rate of cardiac enlargement from chest X-ray and cardiac ultrasound were 45.6%(72/158) and 34.5%(59/171) respectively. The average content of selenium in staple foods(wheat and corn) were[(0.045±0.036), (0.035±0.025)mg/kg, respectively]. The level of hair selenium in patients and healthy people were [(0.376±0.091), (0.384±0.077)mg/kg, respectively], with non-significant different (u=0.77, P>0.05). There were significant differences in whole blood selenium of patients, healthy people in KSD areas and healthy people in non-KSD areas[(0.071±0.017), (0.077±0.017), (0.090±0.016)mg/L, respectively; F=4.55, P<0.05), the whole blood selenium in patients lower than in healthy people in KSD areas (P<0.05), in healthy people in KSD areas lower than in non-KSD areas (P<0.05). Conclusions After the KSD condition being controlled, the situation in Shaanxi Province has become stable and exhibited a decreasing tendency. The selenium level of both internal and external environment in the endemic area increased significantly, that is the main factors of controlling disease.

Objective To explore the status of Keshan disease in Shaanxi province to provide a scientific basis for decision-making of prevention and control of Keshan disease. Methods Nineteen infected villages were randomly selected in 19 infected counties in the range of Keshan disease infected area in Shaanxi province in 2008 as the investigation sites. Clinical examination and electrocardiography were performed in the chosen people at every spots, chest X-ray of posteroanterior position film in 2-meter distance was taken in suspicious cardiac patients, and determining the selenium contents was also determined in the collected grain samples of the investigators. Results Of the 10 228 investigated residents in the endemic area, 110 Keshan disease patients were detected, the total detection rate was 1.08% (110/10 228). Among the 110 patients, 92 were potential Keshan disease, which accounted 0.90%(92/10 228); 18 chronic Keshan disease formed a detection rate of 0.18%( 18/10 228); no acute and sub-acute type of Keshan disease had been inspected. Potential Keshan disease patients often showed electrocardiogram abnormality of complete fight bundle branch block [48.57%(51/105)], ST-T change[ 19.05% ( 20/105 ) ], frequent premature ventricular contraction [ 10.48 % ( 11/105 ) ], left ventricular hypertrophy [ 5.71% (6/105) ], block in the anterosuperior division of the left branch[5.71%(6/105)]; Chronic of Keshan patients mostly presented atrial fibrillation [ 24.00% (6/25) ], left ventricular hypertrophy [ 20.00% (5/25) ], complete right bundle branch block [ 20.00% (5/25)]. The increase rate of cardiothoracie ratio was 18.08% (32/177). Food samples of wheat, corn, millet and rice in infected area residents were of selenium content, being (0.096± 0.028), (0.089 ±0.029), (0.087 ± 0.016), (0.047 ± 0.016)mg/kg, respectively. Conclusions Keshan disease in Shaanxi province is steadily declining, potential and chronic Keshan diseases are currently the main clinical types. Selenium content of food in endemic area has reached the level of the non-endemic area.

The COVID-19 swept across the countries and regions all over the world in the past one year. The marketing of an effective and safe COVID-19 vaccine is expected to control the spread of the disease. A placebo-controlled field efficacy trial is generally considered in the pivotal study of COVID-19 vaccine to observe whether it is able to reduce the incidence rate of the disease effectively. This paper is to introduce and discuss the considerations in study design and the choice of endpoint, statistical evaluation methods, primary estimand choosing and the strategies to various intercurrent events in the COVID-19 efficacy trials.
COVID-19 ; COVID-19 Vaccines ; Humans ; Research Design ; SARS-CoV-2