Source data and its source documents are the foundation of clinical research. Proper source data management plays an essential role for compliance with regulatory and GCP requirements. Both paper and electronic source data co-exist in China. Due to the increasing use of electronic technology in pharmaceutical and health care industry, electronic data source becomes an upcoming trend with clear advantages. To face new opportunities and to ensure data integrity, quality and traceability from source data to regulatory submission, this document demonstrates important concepts, principles and best practices during managing source data. It includes but not limited to: (1) important concepts of source data (e.g., source data originator, source data elements, source data identifier for audit trail, etc.); (2) various modalities of source data collection in paper and electronic methods (e.g., paper CRF, EDC, Patient Report Outcomes/eCOA, etc.); (3) seven main principles recommended in the aspect of data collection, traceability, quality standards, access control, quality control, certified copy and security during source data management; (4) a life cycle from source data creation to obsolete is used as an example to illustrate consideration and implementation of source data management.
China ; Data Collection ; standards ; Documentation ; standards ; Information Storage and Retrieval ; methods ; standards

Animals ; Cardiovascular System ; metabolism ; GTPase-Activating Proteins ; metabolism ; Humans ; Nerve Tissue Proteins ; metabolism ; Signal Transduction

Adult ; Aged ; Carbon Monoxide Poisoning ; blood ; pathology ; Creatine Kinase ; blood ; Female ; Humans ; Male ; Middle Aged ; Myocardium ; pathology ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Troponin I ; blood ; Young Adult

BACKGROUND:Pretreatment is a dominant way to increase the histocompatibility of biomaterials,but many pretreatments are not satisfactory due to some reactions,such as calcification,cytotoxic reaction and reducing the tension resistance.OBJECTIVE:To investigate the effect of immunogenicity,scaffold tension and cell growth factor on the non-pretreated scaffold biomaterials,and to prepare the homograft decellularized scaffolds.DESIGN:Contrast observation for the histomorphology.SETTING:The experiments were carried out in the Department of General Surgery,Affiliated Hospital of Nantong University from June 2006 to March 2007.MATERIALS:Wistar rats of SPF grade were adopted in this study.Sodium dodecyl sulfate from BioteehGrade Company(U.S.A.);basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) from Peprotech Company(UK);dynamometer from Suzhou Electrical Element First Factory (China).METHODS:The vena cava inferior from rats were selected as experimental materials,we decellularized the epithelial cells from vein according to the improved Booth's methods with low osmotic Tris buffer containing sodium dodecyl sulplate,and then reserved the extracellular matrix.After fixing,the decellularized scaffold was stained by hematoxylin and eosin,the collagen fibers were observed and photographed by light microscope and scanning electron microscope.Changes of the intensity of the scaffolds were measured before and after decellularization.The deceilularized scaffolds were transplanted subcutaneously at homogeneity rats to observe whether the scaffolds had induced immunological rejection.In combination with bFGF and/or VEGF,the scaffolds were transplanted subcutaneously at homogeneity rats and took out two weeks later,in order to exam the new vessels in the scaffolds by immunohistochemistry.Dynamometer was applied to compare the change of the intensity of the scaffolds before and after transplantation.MAIN OUTCOME MEASURES:Change of the intensity of the scaffolds after decellularization and transplantation.Formation of new vessels in scaffolds.Local rejection of the scaffold subcutaneously transplanted into rats.RESULTS:The endothelial cells of the vein were completely removed when incubated with Tris buffer containing 0.03% sodium dodecyl sulfate for 48 hours.Results of hematoxylin and eosin staining,light microscope and scanning electron microscope showed that,the main components of extracellular matrix (collagen fiber) were reserved.There was no significant difference in the morphological structure and the intensity of collagenous scaffolds before and after decellalarization (P＞0.05).There was no apparent reject reaction at the embedded site,local incisions healed well.New vessels could be observed in the scaffolds two weeks later.There was no significant difference in the intensity of collagenons scaffolds before and after inoculation (P＞0.05).CONCLUSION:The low osmotic Tris buffer containing 0.03% sodium dodecyl sulfate is suitable for decellularizing the vein.The homograft collagenous scaffolds exhibit no rejection after transplantation,and the intensity of the scaffolds does not descend.VEGF and bFGF can improve the growth of new vessels in the decellularized scaffolds,and have a synergistic effect.

The viable but noncuturable (VBNC) state is a survival strategy when bacteria are exposed to en- vironment stress. The VBNC state is part of the life cycle of non-differentiating bacteria, and it has a far-reaching impact on traditional bacteriology. Cells in the VBNC state fail to grow on the routine bacterio- logical media, here its significance in human health and environment science are detailed. Cells entering the VBNC state exhibit dwarfing and a number of metabolic changes in respiration rates and macromolecular synthesis. This paper summarized the variations in DNA and protein comparing to the culturable cells. We also discussed the ability of cells to resuscitate from the VBNC state and return to an actively metabolizing and culturable form. Some new methods for monitoring the VBNC state were listed. Finally the future was suggested.

Objective: To study the treatment of experimental lung metastasis by intratracheal injection of IL 18 gene recombinant adenovirus. Methods: (1)The mouse IL 18 mRNA was detected by RT PCR, the concentrations of IL 18, associated cytokines in lung lavage and blood were determined by ELISA at different times after intratracheal injection of IL 18 recombinant adenovirus. (2)The lung metastasis nodes, mouse survival period, survival rates were investigated in the treatment of experimental lung metastasis in C57BL/6 mouse model. The NK activity and CTL activity were determined by 51 Cr 4 h release method. Results: (1)The IL 18 mRNA could be detected in lung tissue 6 h after intratracheal use of IL 18 recombinant adenovirus, and the concentrations of IL 18 in lung lavage was higher than that of peripheral blood, and both IL 18 mRNA and IL 18 could not be detected in control groups. (2)Intratracheal use of IL 18 recombinant adenovirus had significant therapeutic effect on experimental lung metastasis with the results of increased CTL and NK activity, and with longer survival period and higher survival rates compared with the control groups. Conclusion: Intratracheal usage of adenovirus vector containing IL 18 gene has therapeutic effect on the lung metastasis, denoting that gene therapy of lung diseases can be done through airway directly with recombinant adenovirus.

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.

Objective To assess the memory function of hyperthyroid patients at different disease durations and investigate the value of cerebral blood flow (CBF) imaging in the detection of memory dysfunction in related regions.Methods Thirty-seven hyperthyroid patients (10 males,27 females; mean age (39.27± 10.58) years) and 28 healthy volunteers (8 males,20 females; mean age (35.80±9.41) years) were enrolled into this prospective study.The patients were divided into two subgroups: short duration group (duration ≤ 6 months; n =15),long duration group (duration ＞6 months ; n =22).Wechsler memory scale was used for memory assessment,and cancellation test was used for attention assessment.Self-rating depressions scale (SDS) and self-rating anxiety scale (SAS) were used for mood disorder assessment.99Tcm-ECD SPECT CBF imaging was performed at rest for all patients and controls on the same day.SPM 2.0 was used to investigate the differences of rCBF between the two groups.Two independent samples t test was used for the comparisons of memory and attention scores between patients and controls,also between patients with short and long disease durations.Multiple stepwise regression was used for factor analysis of memory state.Results Scale total score (92.27±17.50 vs 101.75±11.70; t=-2.476)and memory quotient (91.32±17.76 vs 100.29±9.43 ; t =-2.421) were significant different between patients and controls (both P＜0.05).The scale total score and memory quotient in patients with long disease duration were significant lower than those of controls(88.77±16.69 vs 101.75±11.70,t=-3.231; 86.18±16.73 vs 100.29±9.43,t=3.770,both P＜0.05).The memory quotient was significant lower in patients with long disease duration than those with short disease duration(86.10± 17.13 vs 98.87± 17.00; t =2.212,P＜0.05).There was no significant difference in memory quotient and scale total score between short duration group and controls (t=-0.754,0.910,both P＞0.05).CBF was reduced in the limbic system of hyperthyroid patients and the involved area was larger in patients with long disease duration.Age,attention score,serum FT4 level and reduced CBF in left pulvina nuclei,left lateral geniculate body and right amygdale were the statistically significant factors for impaired memory function in hyperthyroid patients (b=-0.393-0.685,all P＜0.05).Conclusions Memory impairment could be significant in hyperthyroid patients with long disease duration.CBF imaging could reflect the degree of dysfunction at specific brain regions responsible for memory impairment in these patients.

Objective To retrospectively investigate the causes , location and the duration of hospital stays of the hospitalized patients with hard-to-heal wounds so as to provide data guidance for the prevention and research of these diseases. Methods Clinical data of hospitalized patients with hard-to-heal wounds in plastic surgery center of General Hospital of Guangzhou Military Command were collected from June , 2011 to December, 2013. Whether ulceration was recovered in the patients with skin tissue defect after 2 months treatment was regarded as the standard to screen the patients with hard-to-heal wounds. The causes , location, age and the duration of hospital stays of the hospitalized patients with hard-to-heal wounds were investigated by retrospective case-control method. Chi-square test and t-test were used in analyzing the investigation. Results 2 136 cases, aged from 20 to 86, were treated in plastic surgery center of the hospital. 120 cases have hard-to-heal wounds, which constituted 5.62% of all hospitalized patients. (1) Metabolic disease was the main causes of wound (43.3%), followed by wound infection and tumor (20.0% for each) (χ2 = 62.917, P < 0.01). ( 2 ) The peak age for patients with hard-to-heal wounds was 40 to 60 years old patients , followed by patients′age from 60 to 80 years. (3) The mostly like hard-to-heal wounds was on limbs (61.6%), especially on the foot (38.3%) (χ2 = 17.546, P = 0.002). (4) The average days for hospitalization of in the plastic surgery center were (7.41 ± 8.98), while the average days for hospitalization of the patients with years were (33.21 ± 28.27)(t = -9.968, P < 0.05). Conclusion The average diagnostic age of patients with hard-to-heal wounds is the middle and old aged patients. Chronic skin ulcers, which often occurs in a limb, seriously affects a person′s ability to move , which can prolong hospital stays , causing serious burden for the families of patients and the society.