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

CDISC standard has become a set of global data standards that can be used in clinical study, covering the full life cycle of clinical researches. After nearly 20 years of development and continuous version upgrades, CDISC standard can improve the quality and efficiency of clinical research and drug review, and to facilitate all stakeholders involved in researches to exchange the study data and communicate the outcomes. CDISC standard has been or is to be adopted as standard format in data submission by multiple regulatory authorities, and more widely implemented by the global pharmaceutical community. CDISC standard is gradually adopted in China. The feasibility and roadmap of CDISC standard as the Chinese data submission format requirements are undergoing exploration and piloting further.
Biomedical Research ; standards ; China ; Clinical Trials as Topic ; standards ; Data Collection ; standards

Dextroscope workstation is an advanced equipment developed in recent years and isused to make virtual reality model.We not only used it in surgical planning of thyroid disease,but also applied it in clinic teaching.Application of Dextroscope virtual reality system can help to improve students'capabilities of clinical thoughts and clinical techniques,stimulate their learning interest,enlarge the knowledge,shorten learning curve and release the conflict in practice.Dextroscope system will push forward the progress of education reform,so it is worth spreading.

With the deployment of electronic medical records systems, more and more routine clinical data are recorded electronically, which become a potential data source for new drug clinical trials. In this paper, we summarized the opportunities, challenges, obstacles and the latest development in this field.
Clinical Trials as Topic ; Data Collection ; methods ; Drug Evaluation ; Electronic Health Records

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

OBJECTIVELong time exhaled oxygen will induced oxygen toxicity. Some studies had found that different pathology may exised in normobaric and hyperbaric pulmonary oxygen toxicity, and nitric oxide synthase (NOS) may play a role. In this study, we discussed the change of NOS in normobaric and hyperbaric pulmonary oxygen toxicity.

METHODSSixty male SD rats were randomly divided into 6 groups (n = 10), exposed to 1 ATA (atmosphere absolute), 1.5 ATA, 2 ATA, 2.5 ATA and 3 ATA, 100% oxygen for 56, 20, 10, 8, 6 hours respectively. Rats were exposed to air as control. After exposure, the protein in bronchoalveolar lavage fluid (BALF), the wet/dry weight of lung and the expression of eNOS, nNOS in lung were defined.

RESULTSAs compared to air group, the protein in BALF, the wet/dry of lung were significantly elevated in 1.0 ATA group, while these changes were not so obviously in the other groups, and these changes in hyperbaric oxygen group (approximately 1.0 ATA) were significantly decreased as compared with nonnrmobaric oxygen group (1.0 ATA). The expression of nNOS were not changed in normobaric and hyperbaric pulmonary oxygen toxicity, while the expression of eNOS was significantly decreased in 2 ATA group, and significantly elevated in 2.5 ATA and 3 ATA group.

CONCLUSIONThe expression of eNOS can change when exposed to different pressures of oxygen.

Animals ; Disease Models, Animal ; Lung ; metabolism ; Male ; Nitric Oxide Synthase Type I ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Oxygen ; poisoning ; Pressure ; Rats ; Rats, Sprague-Dawley

BACKGROUNDOld pelvis fractures are among the most challenging fractures to treat because of their complex anatomy, difficult-to-access surgical sites, and the relatively low incidence of such cases. Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture. The goal of this study was to assess the use of three-dimensional (3D) printing techniques for surgical management of old pelvic fractures.

METHODSFirst, 16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data. Next, nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models. The pelvic injuries were all type C, and the average time from injury to reconstruction was 11 weeks (range: 8-17 weeks). The workflow consisted of: (1) Printing patient-specific bone models based on preoperative computed tomography (CT) scans, (2) virtual fracture reduction using the printed 3D anatomic template, (3) virtual fracture fixation using Kirschner wires, and (4) preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation. These models aided communication between surgical team members during the procedure. This technique was validated by comparing the preoperative planning to the intraoperative procedure.

RESULTSThe accuracy of the 3D printed models was within specification. Production of a model from standard CT DICOM data took 7 hours (range: 6-9 hours). Preoperative planning using the 3D printed models was feasible in all cases. Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases. The patients were followed for 3-29 months (median: 5 months). The fracture healing time was 9-17 weeks (mean: 10 weeks). No delayed incision healing, wound infection, or nonunions occurred. The results were excellent in two cases, good in five, and poor in two based on the Majeed score.

CONCLUSIONSThe 3D printing planning technique for pelvic surgery was successfully integrated into a clinical workflow to improve patient-specific preoperative planning by providing a visual and haptic model of the injury and allowing patient-specific adaptation of each osteosynthesis implant to the virtually reduced pelvis.

Adolescent ; Adult ; Female ; Fractures, Bone ; diagnosis ; pathology ; Humans ; Imaging, Three-Dimensional ; methods ; Male ; Middle Aged ; Pelvic Bones ; surgery ; Reconstructive Surgical Procedures ; Young Adult

OBJECTIVETo evaluate the value of magnetic resonance dynamic contrast-enhanced (MR-DCE) and magnetic resonance diffusion-weighted imaging (MR-DWI) in the differentiation of benign and malignant musculoskeletal tumors.

METHODSSixty-three patients with pathologically confirmed musculoskeletal tumors were examined with MR-DCE and MR-DWI. Using single shot spin echo planar imaging sequence and different b values of 400, 600, 800 and 1000 s/mm(2), we obtained the apparent diffusion coefficient (ADC) of the lesions. ADC values were measured before and after MR-DCE, with a b value of 600 s/mm(2). The 3D fast acquired multiple phase enhanced fast spoiled gradient recalled echo sequence was obtained for multi-slice of the entire lesion. The time-signal intensity curve (TIC), dynamic contrast-enhanced parameters, maximum slope of increase (MSI), positive enhancement integral, signal enhancement ratio, and time to peak (T(peak)) were also recorded.

RESULTSADC showed no significant difference between benign and malignant tumors when the b value was 400, 600, 800, or 1000 s/mm(2), and it was not significantly different between benign and malignant tumors in both pre-MR-DCE and post-MR-DCE with b value of 600 s/mm(2). TIC were classified into four types type1 showed rapid progression and gradual drainage; type2 showed rapid progression but had no or slight progression; type 3 showed gradual progression; and type 4 had no or slight progression. Most lesions of type1 or type2 were malignant, whereas most lesions of type 3 or type 4 were benign. When using type1 and type 2 as the standards of malignancy, the diagnostic sensitivity and specificity was 87.23% and 50.00%, respectively. The types of TIC showed significant difference between benign and malignant musculoskeletal tumors(χ(2)=17.009,P=0.001). When using MSI 366.62 ± 174.84 as the standard of malignancy, the diagnostic sensitivity and specificity was 86.78% and 78.67%, respectively. When using T(peak)≤70s as the standard of malignancy, the diagnostic sensitivity and specificity was 82.89%and 85.78%, respectively. Positive enhancement integral and signal enhancement ratio showed no significant difference between benign and malignant musculoskeletal tumors.

CONCLUSIONSTIC, MSI and T(peak) of MR-DCE are valuable in differentiating benign from malignant musculoskeletal tumors. T(peak) has the highest diagnostic specificity, and TIC has the highest diagnostic sensitivity. The mean ADC value are no significant difference between benign and malignant tumors.

Adolescent ; Adult ; Aged ; Bone Neoplasms ; diagnosis ; Child ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Muscle Neoplasms ; diagnosis ; Young Adult

OBJECTIVETo investigate the effects of transfection of agrin gene on the recovery of muscle function after a free neurovascular muscle transfer.

METHODSThe electrical gene transfection was performed when the gracilis muscle of the SD rat was completed free neurovascular transfer. The experimental group was treated with pCS2+ -agrin, the group with plasmid pCS2+ as the negative control and the group with normal saline as the frank control. The muscle function, expression of neural agrin and the junctional nAChR number was measured after the operation.

RESULTSAt 4, 5 and 10 weeks postoperatively, the pCS2+ -agrin group was significantly better than the control groups in muscle function (P < 0.05 ). The immunohistochemical staining showed an increasing deposition of the agrin protein near the endplate at 1 and 5 weeks after the operation, but decreasing remarkably to the level of control groups at 10 weeks postoperatively. The pCS2+ -agrin group was significantly more than the control groups in junctional nAChR number at every points of the time postoperatively.

CONCLUSIONSTransfection of agrin gene in the transferred muscle may increase the early recovery of muscle function.

Agrin ; genetics ; Animals ; Female ; Genetic Therapy ; Genetic Vectors ; Muscle Proteins ; genetics ; Muscle, Skeletal ; transplantation ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Transfection

OBJECTIVETo compare antiproliferation effects of vinblastine nanopraticles and vinblastine water solution in human glioma cell lines BT325.

METHODVinblastine nanoparticles were prepared by emulsion polymerization process and using dextran as a stabilizing agent. It was characterized by means of morphology, size, drug entrapment efficiency and loading efficiency. Human glioma cell lines BT325 were treated with different concentrations of vinblastine nanoparticles and vinblastine water solution for 48 h, Antiproliferation effect was measured by MTT method. Morphological changes were observed by inverted microscope, transmission electron microscope and scanning electron microscope.

RESULTMean diameter of VLB-PBCA-NP was about 74.4 nm, and drug entrapment efficiency and loading efficiency was 78.47% and 39.24%, respectively. Cell growth inhibition rate of vinblastine nanoparticles group and vinblastine water solution group in a concentration range (5-5 000 g x L(-1)) for 48 h was 41%, 49%, 73%, 83% and 28%, 33%, 54%, 60% respectively. Entrapment of VLB in NPS may distinctly degrade absorbency as compared to free drugs. Glioma cell BT325 which treated with VLB water solution were initial stage of apoptosis, and apoptosis body were forming. But VLB NPS-treated BT325 cells were intermediate or end stage, and missed structure integrality.

CONCLUSIONVLB-PBCA-NP and VLB water solution could inhibit the growth of human glioma cell lines BT325, and VLB nanoparticles have stronger inhibition effect compared with VLB water solution in the same dose. PBCA may be effective as promising carrier for the transport of vinblastine into the glioma cells.

Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Microscopy, Electron, Transmission ; Nanoparticles ; Vinblastine ; pharmacology