Objective To explore the biomechanical mechanism of pseudoaneurysm formation at the anastomotic site of vascular patch and the inhibitory effect of transforming growth factor(TGF β1)hydrogel on aneurysm.Methods The vascular patch model and the pseudoaneurysm model were constructed separately,and the two-way fluid-structure interaction method was used to numerically simulate the blood-vessel wall dynamic response at the anastomosis.Based on the analysis of mechanical parameters such as postoperative blood velocity,vessel wall shear stress and aneurysm wall displacement,the mechanisms of postoperative pseudoaneurysm formation and inhibition were studied.Results The numerical simulation results showed that the wall shear stress increased when the blood flowed through the front end of the patch.When the pseudoaneurysm has been formed after surgery,the aneurysm wall became significantly thicker following the injection of TGF β1 hydrogel into the aneurysmal wall,and the intratumoral shear stress and the aneurysmal wall displacement were decreased.Conclusion Pseudoaneurysms are easy to form at the front end of the anastomosis after surgery,and the injection of TGF β1 hydrogel into the aneurysm wall can effectively inhibit the formation and progression of pseudoaneurysm.The numerical simulation study provides a numerical basis for the mechanical mechanism study of the formation and progression of pseudoaneurysm after patch angioplasty.

BACKGROUND: Zero-P anterior cervical fixation system is an important means for treatment of cervical myelopathy in recent years. Zero-P fixation system can achieve effective decompression of spinal cord and nerve, and restore cervical curvature, with good stability.OBJECTIVE: To investigate the biocompatibility of Zero-P for multilevel cervical myelopathy.METHODS: Totally 62 patients with multilevel cervical disease who were treated by anterior cervical discectomy and fusion with Zero-P were selected, including double segments in 47 cases, three segments in 13 cases and four segments in 2 cases. Clinical efficacy was evaluated by pain visual analogue scale score, Japanese Orthopedic Association score, neck disability index score at postoperative 1, 6, 12, 24 months. Simultaneously, incidence of postoperative complications, cervical intervertebral space height and Cobb angle changes were observed.RESULTS AND CONCLUSION: (1) 54 patients were followed 2 years after treatment by clinic or telephone. Mean operative time was (102.00±32.41) minutes; average blood loss was (62.45±18.36) mL. (2) Two patients affected mild throat discomfort at one day after operation, and the symptoms went to lift six days after. The remaining patients did not experience any other complications. (3) Visual analogue scale score and neck disability index score at 1, 6, 12 and 24 months after operation were all less than preoperatively (P < 0.05); Japanese Orthopedic Association scores were higher than preoperatively (P < 0.05); the Cobb angle was improved significantly and greater than before treatment (P < 0.05).Postoperative cervical intervertebral space height was significantly higher than preoperatively (P < 0.05). Japanese Orthopedic Association results showed that among 54 patients, excellent was found in 34 cases, good in 14 cases,average in 6 cases and poor in 0 cases; the excellent and good rate was 89%. (4) Zero-P has a good clinical efficacy for multilevel cervical myelopathy, relieves symptoms significantly and restores cervical curvature and height, and has a good biocompatibility.

BACKGROUND: Bushen Huoxue Tongluo Capsule, a well-known traditional prescription, exhibits remarkable treatment outcomes in knee osteoarthritis, but the underlying mechanism is not fully understood. OBJECTIVE: To explore the regulatory effect of Bushen Huoxue Tongluo Capsule on miR-27a of synovial cells in Sprague-Dawley rats with knee osteoarthritis. METHODS: The model of knee osteoarthritis was established in 120 Sprague-Dawley rats using Hulth method, and then these rat models were randomized into four groups, followed by given75 mg/kg normal saline (blank control group), 34 (low-dose group), 75 (medium-dose group) and 140 (high-dose group) mg/kg Bushen Huoxue Tongluo Capsule aqueous solvent via gavage according to body mass, respectively, twice daily, for consecutive 2 courses (15 days as a course) with 2 days in between. The synovium and cartilages were removed after each course, and the expression of miR-27a in the knee joint synovium and chondrocytes was determined by real-time quantitative PCR. RESULTS AND CONCLUSION: Gross observation found that the degeneration of synovium and cartilage in the Bushen Huoxue Tongluo Capsule groups was milder than that in the blank control group. Real-time PCR revealed that there was an increasing trend in the expression of miRNA-27a in the synovium and cartilage in each group, especially in the high-dose group, and there was a significant difference between groups (P < 0.05). Our findings show that Bushen Huoxue Tongluo Capsule can suppress the reduced expression of miRNA-27a in the synovium and chondrocytes in rats with knee osteoarthritis, further alleviating knee degeneration and protecting the knee from damage.

BACKGROUND:Different anesthesia methods significantly impact mean arterial pressure, systolic and diastolic blood pressure, arterial blood pH and blood viscosity, but what kind of anesthesia method is more suitable for preparation of animal model does not reach an agreement. OBJECTIVE: To compare the effectiveness of local anesthesia and general anesthesia for preparation of rabbit intervertebral disc degeneration model in procession of percutaneous acupuncture rotary cut. METHODS:A total of 48 New Zealand white rabbits were randomly divided into the local anesthesia group and the general anesthesia group. The local anesthesia group was anesthetized with 0.5% lidocaine. The general anesthesia group was intraperitoneally injected with 3% sodium pentobarbital (30 mg/kg). In the two groups, models of intervertebral disc degeneration were established by minimally invasive percutaneous acupuncture rotary cut at L4/5, L5/6 levels. Modeling time was observed in both groups. Disc degeneration was evaluated by the gross observation, MRI detection, and histopathological examination at 4, 8, 12, and 16 weeks after modeling. RESULTS AND CONCLUSION: (1) General observation: the nucleus pulposus gradually with darker color and elasticity reduced in two groups after modeling. (2) MRI T2-weighted image results showed no significant changes in disc signal intensity at early stage, but the signal strength showed a decreasing trend with time. (3) Disc degeneration was evaluated according to Pfirrmann grading. Disc degeneration was gradually increased with time in two groups (P< 0.05), but there was no significant difference at postoperative time points in both groups (P > 0.05). (4) Masson staining showed that different degrees of annulus irregular arrangement appear in the two groups 8 and 12 weeks after modeling, but the structure was still intact. 16 weeks later, annulus disorganized, or even breakage in the two groups; no significant difference was detected between the two groups. (5) Safranin O staining showed that nucleus pulposus cells were not significantly reduced in the two groups at 4 weeks, but were significantly reduced at 16 weeks. (6) The average modeling time of local anesthesia group [(15.24±2.67) minutes] was significantly shorter than that in the general anesthesia group [(25.64±6.85) minutes] (P < 0.05). These results indicate that intervertebral disc degeneration model can be successfully established by minimally invasive percutaneous acupuncture rotary cut by using local anesthesia and general anesthesia; however, local anesthesia has a shorter operating time and simple anesthetic procedure. The efficacy was identical between the two methods.

BACKGROUND:The Herbal Compound formula Yaotu Granules for lumbar disc degeneration has achieved satisfactory efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To explore the possible molecular mechanisms ofYaotu Granules for lumbar disc degeneration based on transcriptome sequencing (RNA-seq). METHODS: Ten New Zealand white rabbits were randomly divided into control and experimental groups (n=5 per group), followed by intragastric injection of 20 mL of normal saline and 20 mL of water decoction of Yaotu Granules, respectively, twice daily for consecutive 1 week. The different drug serums were prepared using serum samples obtained from the common carotid artery at 2 hours after the last injection. Human nucleus pulposus cells were cultured in DMEM containing 10% different drug serums to observe the cellular morphology in each group. The cell viability was detected by trypan blue staining. The passage 3 human nucleus pulposus cells were pretreated for 48 hours, the mRNA level was detected using RNA-seq, and the differentially expressed mRNA was screened by RNA-seq. Subsequently, the differential gene expression, Gene Ontology (GO) enrichment analysis and Pathway enrichment analysis were performed. RESULTS AND CONCLUSION: In the experimental group, there were round or fusiform cells with abundant cytoplasm and clear nuclei that showed smooth surface and complete nuclear membrane; elongated rough endoplasmic reticulum arranged regularly, and less mitochondrion, scattered lysosomes and filaments were visible in the cytoplasm. In the control group, spindle and polygonal cells were found, and the large nuclei with 2 or 3 nucleoli and slightly rough surface were observed; there were mildly dilated endoplasmic reticulum, and few mitochondria with incomplete membrane. The adherent rate, generation time and cell viability of passage 1, 2 and 3 cells in the experimental group were significantly better than those in the control group (P < 0.05). Sequencing results found that there were 464 differentially expressed genes including 143 upregulated, and 321 downregulated genes. GO analysis revealed that the differentiated genes were mainly concentrated on cell regulation and metabolism. Pathway analysis found that mainly differentiated genes focused on the metabolism related pathways. These findings suggest that the differentially expressed gene profile of Yaotu Granules for lumbar disc degeneration is obtained by RNA-seq technology.Yaotu Granules mainly upregulate extracellular matrix metabolism-related genes and downregulate polysaccharide synthesis related genes in the prevention and treatment of lumbar disc degeneration, which provides basis for further research.

This list of clincal data management documentation is to ensure standardized and adequate archival of trial documents and records in clinical data management, which is applicable to all of phase I-IV clinical trials.

ICH GCP requires that all information of clinical trial should be recorded, processed, and stored in a way that allows the accurate reporting, interpretation and verification. A trial master file (TMF) contains all paper or electronic records/documentations related to a clinical trial. As a tool of the retrospective analysis, the TMF profile should be able to reproduce the full procedure of the trial completely. As a part of TMF profiles, both the accuracy and completeness of clinical data management documentation are important in data integrity. It is helpful to learn the workflow of clinical data management in different stage of a clinical trial, to understand which documents are essential, and why the documentation of clinical data management is important for data integrity. This paper elaborates how to perform the good documentation practice of clinical data management, and suggests that both the precise and efficient document management and regular quality control may ensure the high quality of clinical data documentation management on the basis of an intensive awareness of the overall process of clinical data management.

A perfect clinical trial must nave a solid study design, strict conduction, complete quality control, non-interference of statistical result, and acceptable risk-benefit ratio. To reach the target, the quality control (QC) should be performed from the study design to conduction, from the analysis to conclusion. We discuss the relationship between data management and biostatistics from the statistical point of view, and emphasize the importance of the statistical concept and methods in the improvement of data quality in clinical data management.

The quality and integrity of clinical trials and associated data are not only derived from accuracy of trial data analyses, but also closely embodied to the authenticity and integrity of those data and data documents as well as the compliant procedures obtaining those data and relevant files in the life cycle of clinical trials. The compliances of good clinical practices and standards suggest the reliability, complete and accuracy of data and data documents, which is constructing the convincible foundation of drug efficacy and safety validated via clinical trials. Therefore, the monitoring and auditing on clinical trials and associated data quality keep eyes on not only verifications of reliability and correctness on the data analytic outcomes, but also validation of science and compliance of the trial management procedure and documentations in the process of data collections.

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.