Implementation of information technology in clinical research has resulted in revolutionary changes in drug development. Based on the good clinical practice (GCP) requirements on data, processes and documentations, and the era of fast growth in clinical studies using up-to-date information technology, we explore an integrated e-clinical solution in clinical studies in China.
China ; Clinical Trials as Topic ; Data Collection ; methods ; Medical Informatics ; methods

Adult ; Burkitt Lymphoma ; metabolism ; pathology ; CD3 Complex ; metabolism ; DNA Nucleotidylexotransferase ; metabolism ; Diagnosis, Differential ; Female ; Granulosa Cell Tumor ; metabolism ; pathology ; Humans ; Ki-67 Antigen ; metabolism ; Leukocyte Common Antigens ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; surgery ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; surgery ; Sarcoma, Myeloid ; metabolism ; pathology

On-line analysis and control are critical for the optimization of product yields in animal cell culture. The close monitor of viable cell number helps to gain a better insight into the metabolism and to refine culture strategy. In this study, we use the oxygen uptake rate (OUR) to estimate the number of viable cell and the OUR-based feed-back control strategy for nutrients feeding to improve the efficiency of cell culture. A hybridoma cell line (HAb18) was cultured in fed-batch and perfusion model using serum free medium in 5L CelliGen Plus bioreactor (NBS Co., American) and 5L Biostat B bioreactor (Braun Co., Germany). The system and the method for online monitoring OUR in bioreactors, based on the dynamic measurement of dissolved oxygen (DO), were developed. The method of on-line cell concentration estimation was established based on the relationship between the growth of the hybridoma and the uptake rate of oxygen. This method was then used to determine OUR and the concentrations of cell, antibody, glucose, lactate, glutamine and ammonia in the bioreactors at given times. The relationship between OUR and nutrients metabolism was studied and OUR-based feed-back control strategy, which used the state deltaOUR = 0 as the regulation point, was established and used to control the rates of nutrients or medium feeding rate in the perfusion culture. The results showed that there was close relationship between OUR, concentration of live cells, productivity of antibody and consumption of glutamine. The sudden decrease in OUR may be caused by glutamine depletion, and with different delay times, the viable cell concentration and antibody productivity also decreased. The further analysis revealed the linear relationship between OUR and the density of live cells in the exponential growth phase as qOUR = (0.103 +/- 0.028) x 10(-12) mol/cell/h. These findings can be applied to the on-line detection of live cell density. Our study also indicated that by adjusting the perfusion rate with OUR-based feed-back control strategy, it is feasible to continuously increase in viable cell density and antibody concentration in the perfusion culture.
Bioreactors ; Cell Culture Techniques ; methods ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Hybridomas ; metabolism ; Oxygen ; metabolism

Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several myeloid cells, induces G1 phase arrest in many cell lines. In this study, we investigated the possibility of using DMSO to arrest H18 hybridoma cells to the G1 phase and monitor whether the arrest improves antibody production. We showed that DMSO in concentration ranging between 0.3% and 0.6% efficiently arrested H18 hybridoma cells in G1 phase. In our experiment, > 80% of cells grown for 36h in presence of the 0.6% DMSO were arrested in G1. Furthermore, expression levels of P27 were up-regulated tow fold during the G1 phase. Higher concentration of DMSO at 0.9% leads to cytotoxicity. Herein we show a simple way, a two-stage process for antibody production, which consists of a proliferation phase leading to the desired cell density, followed by an extended production phase during which the cells remain at G1 phase. Our observation that the addition of DMSO results in increase antibody production is of significance in further use of hybridoma cells in high density large scale cell culture.
Animals ; Antibodies, Monoclonal ; biosynthesis ; Cell Proliferation ; drug effects ; Dimethyl Sulfoxide ; pharmacology ; G1 Phase ; drug effects ; Hybridomas ; drug effects ; immunology ; Mice ; Proliferating Cell Nuclear Antigen ; analysis

Objective To identify the epidemic characteristics and risk factors of an emerging infectious disease-severe fever with thrombocytopenia syndrome (SFTS) in Hubei province.Methods Active surveillance program on SFTS was set up in monitoring sites-hospitals,at the township level or above,in Suizhou,Huanggang and Wuhan from January to December,2010.Specific surveillance program on SFTS was launched across the province in hospitals above the county level.Cases that matched the definition of surveillance case were identified and reported to Centers for Disease Control and Prevention (CDCs).Cases were interviewed and their blood samples collected and detected using PCR and virus isolation.We also conducted serum antibody surveys among healthy population and livestock and surveillance on vector ticks in those high-epidemic areas.Results 188 cases that matched the definition of surveillance case and 21 deaths were reported in 11 cities,32 countries and 100 towns in 2010,with an incidence rate of 0.33/106.The fatality rate was 11.2％.Data showed that the patients were from hilly areas at the altitude elevated between 28-940 meters.The epidemic period was between April and December with the peak from May to September.The youngest case was an 11-year old,while the eldest was 81 with median age as 56-year old.95.3 ％ of the patients were farmers.All Patients did not have the history of traveling,two weeks before the onset of SFTS.93.6％ of the patients engaged in different kind of work which was associated with agriculture.52.8％ of the patients had been exposed to ticks.22.0％ of the patients had been bitten by ticks.Skin injury was found in 64.2％ of the patients.Samples from 129 cases (68.6％) were collected and detected,with 67.4％ of them (87 cases) showed positive by Real time-PCR for SFTS virus.An elevation in antibody titer by a factor of four or evidence of sero-conversion was observed in 11 patients; SFTS virus was isolated from 2 patients.The total antibody positive rates were 3.8％,55.0％ (6/11 ),36.7％ (2/3) and 80.0％ (4/5) respectively in healthy population,dogs,sheep and cows.Ticks from grass,cattle and sheep were detected positive by Real time-PCR.Conclusion Most cases of SFTS in Hubei were infected by SFTS virus,and cases of livestock were infected by SFTS virus.Ticks might serve as an important vector.Skin injury,exposure to tick bites seemed to be the risk factors.

To understand the maintenance and transmission of SFTS virus, the potential vector ticks were collected from sheep, cattle and dogs in the endemic areas of SFTSV in Shandong Province. Among the collected ticks, the dominant species was H. longicornis ticks. Real-time PCR for RNA detection, virus isolation and characterization, genomic sequencing, phylogenetic and antigenic analysis were performed in this investigation. The results showed that the SFTS viral RNA was detected in 2.14% H. longicornis, and a SFTS virus was isolated from one of viral RNA positive ticks collected from sheep. Whole genome analysis of the SFTSV isolates with 11 human-origin SFTS virus revealed a highly pairwise similarity, and the growth curve analysis showed nearly identical in virus yield and the dynamic of virus reproduction compared to human derived viral isolates. Immunofluorescence and neutralization test showed identical serological reaction character of the two different origin viral strains. In this study, the characters of a SFTSV isolate was firstly described, which suggested that the tick species H. longicornis acting important vector role in the transmission of SFTS virus.
Animals ; Animals, Domestic ; parasitology ; Arachnid Vectors ; virology ; Bunyaviridae Infections ; transmission ; virology ; Cattle ; Cell Line ; Dogs ; Humans ; Livestock ; parasitology ; Molecular Sequence Data ; Phlebovirus ; classification ; genetics ; isolation & purification ; Phylogeny ; Sheep ; Ticks ; virology