For pharmaceutical industries, clinical data is one of the most valuable deliverables. It is also the basis of analysis, submission, approval, labeling and marketing of a drug product. To ensure the integrity and reliability of clinical data, a scientific standardized quality control (QC) has to be established at each step of a clinical trial. Data validation is conducted to ensure the reasonability and compliance of clinical data by checking data quality before the data is statistically analyzed. This paper focuses on purpose of data validation, creation of data validation plan, rationale of data validation, types of data validation and performance of user acceptance testing on clinical database.
Clinical Trials as Topic ; standards ; Data Accuracy ; Data Collection ; standards ; Databases, Factual ; Quality Control ; Reproducibility of Results

Granulocyte Colony-Stimulating Factor ; immunology ; pharmacology ; therapeutic use ; Humans ; Liver Failure ; immunology ; therapy

ObjectiveTo investigate the effect of age and gender on the position of termination of the conus medullaris (CMT).MethodsOne thousand three hundred and thirty-nine patients aged 4-89 yr scheduled for lumbar magnetic resonance imaging examination were selected.The position of CMT was determined using Visart 1.5 T or Magnetom Trio 3.0 T magnetic resonance imaging instrument.Results Five hundred and ninety-four male patients and 745 female patients were enrolled in the study.There was no significant difference in the percentage of CMT located at the L2,3 intervertebral disc level between female (1.2％) and male (0.5％) patients (P＞0.05),and female patients had a lower mean CMT than male patients (P＜0.01).There was no correlation between age and mean CMT in patients aged ≤19 yr (P＞ 0.05).There was a positive correlation between age and mean CMT in female patients aged≤20 yr (r =0.076,P＜0.05),but there was no correlation between age and mean CMT in male patients aged ≤ 20 yr (P＞0.05 ).ConclusionFemale patients have a lower mean CMT than male patients,and there is still a risk when performing spinal anesthesia,although the probability that CMT located at the L2,3 intervertebral disc level is low in female and male patients.The position of CMT is lower with increased age in adult female patients,but it is not related to age in adult male patients.

Adult ; Humans ; Male ; Maxillary Sinus ; Xanthogranuloma, Juvenile

OBJECTIVE:To determine the contents of citric acid in fentanyl citrate raw materials and its injection by ion chro-matography. METHODS:The determination was performed on Thermo Dionex IonPacTM AS11-HC column with mobile phase con-sisted of potassium hydroxide (gradient elution) at the flow rate of 1.0 mL/min. The column temperature was 35 ℃,and sample size was 20 μL. The detector was suppressed conductivity detector. RESULTS:The linear range of citric acid were 0.1157-74.05 μg/mL(r=0.9995). The limit of quantitation was 0.1150 μg/mL,and the limit of detection was 0.0400 μg/mL;RSDs of preci-sion,stability and reproducibility tests were all lower than 2.0%;the average recoveries were 99.6%-101.5%(RSD=0.68%,n=9). CONCLUSIONS:The method is environmentally-friendly and simple with good accuracy and precision,and suitable for the contents determination of citric acid in fentanyl citrate raw materials and injection.

This study aims to perform a survey of genetic variation in neuraminidase (NA) gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors, in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino acid sequences was performed by MEGA 4.0. Phylogenetic trees were also constructed. Strains isolated during 2010-2011 in this study clustered closely with World Health Organization (WHO) 2010-2012 reference vaccine strain A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the phylogenetic tree, while the 2012 isolates were located on another branch. In analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the 2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K, P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a glycosylation site to the activity center of NA. No significant variation was discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of 2012 were found with significant mutation, which has the potential of inducing minor resistance to NA inhibitors like zanamivir and oseltamivir.
Amino Acid Sequence ; China ; Humans ; Influenza A Virus, H3N2 Subtype ; classification ; enzymology ; genetics ; isolation & purification ; Influenza, Human ; virology ; Molecular Sequence Data ; Neuraminidase ; chemistry ; genetics ; Phylogeny ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics

Objective To investigate the influence of S100A6 gene RNA interference on the biological behaviors of A549 lung adenocarcinoma cells.Methods The S100A6 gene RNA interference vector was transfected in A549 lung adenocarcinoma by lentivirus.The experiment was divided into three groups:pLenR-GPH group (the vector without S100A6 RNAi gene was transfected),negative control group (no vectors was transfected),and RNAi group (the vector with S100A6 RNAi gene was transfected).S100A6 mRNA and protein were detected using real-time PCR and Western blotting.The biological behavior including cell proliferation,invasion,cell cycle and cell apoptosis were detected by 3-(4,5-dimethyl-2-thiazoly)-2,5-diphenyl-2H-tetrazolium bromide,transwell,and flow cytometer,respectively.Results The expression of S100A6 mRNA of A549 lung adenocarcinoma cell line in RNAi group (0.009 ± 0.001) was significantly decreased than those in negative control group (0.049 ± 0.005) and pLenR-GPH group (0.030 ± 0.006),with statistically significant differences (t =57.56,P =0.000;t =48.21,P =0.000).The expression of S100A6 protein of A549 lung adenocarcinoma cell line in RNAi group (0.107 ± 0.002) was significantly decreased than those in negative control group (0.341 ± 0.005) and pLenR-GPH group (0.311 ± 0.006),with statistically significant differences (t =37.34,P =0.000;t =27.51,P =0.001).The ability of cell proliferation at 48 hours in RNAi group (0.230 ± 0.008) was significantly declined than those in negative control group (0.292 ± 0.038) and pLenR-GPH group (0.307 ± 0.013),with statistically significant differences (t =25.31,P =0.003;t =29.42,P =0.001).The number of transmembrane cells in RNAi group (11.40 ± 1.36) was significantly declined than those in negative control group (26.80 ± 1.83) and pLenR-GPH group (25.80 ± 1.93),with statistically significant differences (t =29.44,P =0.001;t =23.17,P =0.005).The cell proportion of S phase in RNAi group (28.26％ ± 0.38％) was significantly lower than those in pLenR-GPH group (44.73％±0.66％) and negative control group (45.15％ ± 1.69％),with statistically significant (t =63.69,P=0.000;t =71.55,P =0.000).Cell propotion of G2-M phase in RNAi group (26.99％ ± 0.29％) was signi-ficantly higher than those in negative control group (13.26％ ±0.49％) and pLenR-GPH group (12.41％ ± 0.46％),with statistically significant (t =56.31,P =0.000;t =51.39,P =0.000).The cell apoptosis proportion in RNAi group (8.90％ ±0.48％) was significantly higher than those in negative control group (5.84％ ±0.21％) and pLenR-GPH group (5.99％ ±0.37％),with statistically significant (t=51.34,P =0.000;t =47.27,P =0.000).Conclusion S100A6 gene involves the proliferation,invasion,cell cycle and apoptosis of tumor cells,which has close correlation with occurrence,development and metastasis of lung adenocarcinoma.S100A6 gene is hopeful to become a molecular target for the diagnosis and treatment of lung adenocarcinoma.

Objective To investigate the expression of sodium iodide symporter (NIS ) mRNA in differentiated thyroid Carcinoma (DTC)and further explore its value in clinical diagnosis and therapy of DTC. Methods The expression of NIS mRNA was detected and analyzed in 21 nodular goiter and 45 cases of DTC (including 35 cases of papillary thyroid carcinoma and 10 cases of follicular thyroid carcinoma)by using real-time fluorescent quantitative reverse transcription polymerase chain reaction (real-time RT-PCR).Results Compared with that in nodular goiter,the mRNA expression of NIS in DTC tissue was significantly decreased (P < 0.05 ). Moreover,the mRNA expression of NIS was significantly correlated with lymph node metastasis and AJCC stage, respectively.The expression of NIS mRNA in DTC with lymph node metastasis was significantly decreased compared with that in DTC without lymph node metastasis (P <0.05).In addition,the expression of NIS mRNA in Ⅱ-Ⅳstage DTC was significantly decreased compared with that in Ⅰ - Ⅱ stage DTC (P < 0.05 ).Conclusion Differential expression of NIS can provide evidence for individual 1 3 1 I therapy for DTC.

BACKGROUND:Various factors can affect the osteogenic differentiation of human adipose-derived stem cel s, and the osteoinductive factor of traditional Chinese medicine is very important for the research of human adipose-derived stem cel s. OBJECTIVE:To investagate the effects of ginsenoside Rb1 on the proliferation and osteogenic differentiation of human adipose-derived stem cel s in vitro. METHODS:The human adipose-derived stem cel s were isolated and cultured in vitro. After passaqed to the third generation, human adipose-derived stem cel s at 2×103/wel were incubated in a 96-wel plate, and treated with 200μL of 0.5, 1.0, 2.0, 4.0,6.0μmol/L ginsenoside Rb1 medium. The human adipose-derived stem cel s in the control group were treated with an equal volume of Dulbecco’s modified Eagle medium. Growth curves were examined by 2,3-bis-(2-methoxy-4-nitro-5-sulphenyl)-(2H)-tetrazolium-5-carboxanilide T colorimetric assay. Alkaline phosphatase activity and osteocalcin content were detected by alkaline phosphatase kit and radio-immunity method, respectively. Calcified nodules were observed using alizarin red O staining. RESULTS AND CONCLUSION:The proliferation viability of human adipose-derived stem cel s was significantly increased after cultured with 0.5μmol/L ginsenoside Rb1. With the increasing of the concentration of ginsenoside Rb1, the mitogenic activity of the cel s was decreased. The 6.0μmol/L ginsenoside Rb1 showed a depressant effect on proliferation. Ginsenoside Rb1 could promote alkaline phosphatase activity and osteocalcin expression in human adipose-derived stem cel s and showed a dose-dependent manner. Calcified nodule formation induced by 4.6 and 6.0μmol/L ginsenoside Rb1 were better when compared with 0.5, 1.0 and 2.0μmol/L ginsenoside Rb1. Ginsenoside Rb1 can promote the proliferation of human adipose-derived stem cel s cultured in vitro in a certain concentration, and in the high concentration, the ginsenoside Rb1 can promote the osteogenic differentiation of human adipose-derived stem cel s. So ginsenoside Rb1 can be used as an osteoinductive factor.

Wound secretion from 20 patients with gaseous gangrene was collected for Gram staining,bacterial culture and drug sensitivity tests.The results indicated that gaseous gangrene was caused by the co-infection of both aerobic and anaerobic bacteria.Gram-negative bacilli were slishtly more common than other aerobic bacteria in gageous gangrene wound,which was different from the findings of ordinary gaseous gangrene.