Objective To investigate the clinical significance of the miR-543/syntrophin beta 1(SNTB1)axis in colorectal cancer(CRC)and its influence on the tumor immune microenvironment.Methods The expression of SNTB1 in CRC tissues was analyzed using public data,such as,The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx),and Human Protein Atlas(HPA).Then Kaplan-Meier survival analysis,univariate Cox regression analysis and correlation analysis were performed to evaluate the prognostic value of SNTB1 and its relationship with immune microenvironment in CRC.The targeting relationship between miR-543 and SNTB1 was confirmed through online databases and fluorescence assays in HT-29 cells.For in vitro experiments,after transfecting si-SNTB1,miR-543 mimics and/or SNTB1 overexpression plasmids,HT-29 cells were co-cultured with CD8+T cells,the expression of miR543 and SNTB1 and the viability and cytotoxicity of CD8+T cells were assessed with qRT-PCR,Western blotting,flow cytometry,ELISA,and lactate dehydrogenase(LDH)release assay.Results Analysis of public databases revealed significantly higher expression of SNTB1 in CRC tissues than normal tissues(P<0.001).The CRC patients with high SNTB1 expression exhibited poorer prognosis when compared with those with low expression level(P<0.05).Moreover,high SNTB1 expression was negatively correlated with immune scores in the tumor microenvironment and immune cell infiltration,especially CD8+T cells(P<0.05).Furthermore,Knockdown of SNTB1 in HT-29 cells enhanced the cytotoxic activity of CD8+T cells(P<0.01).Online database and in vitro experiments confirmed that miR-543 targets SNTB1,while the expression of miR-543 was decreased in colorectal cancer(P<0.001).Transfection with the miR-543 mimic inhibited the expression of SNTB1 in HT-29 cells(P<0.001),while overexpressing SNTB1 counteracted the promotion effect of miR-543 mimics on CD8+T cell-mediated cytotoxicity(P<0.05).Conclusion MiR-543 activates CD8+T cells and enhances their cytotoxicity against HT-29 cells by directly targeting SNTB1.

Objective:In response to the current situation where Investigator-Initiated Trial (IIT) management system of pediatric medical institutions in our country is inadequate and the management of high-risk projects needs to be strengthened, a pediatric hospital in Beijing has been selected as a pilot to develop a system and process suitable for IIT management. We aim to explore personalized management models for different types of research projects, especially high-risk ones, to improve the quality of pediatric IIT, reduce research risks, and enhance management efficiency.Methods:By analyzing the current management situation of high-risk pediatric IIT, optimization strategies were proposed to improve the internal IIT project management system and processes of the pilot unit, and effective management measures are promoted.Results:By revising the IIT project management system, improving the project application and approval processes, strengthening process quality control and personnel training, the risk control and quality supervision of such projects had been enhanced, thereby improving project quality and ensuring the rights and interests of research participants.Conclusions:After the pilot unit trialed a series of management measures for high-risk IIT projects, researchers' risk awareness has significantly increased, and project quality has been effectively improved. The Results provide a reference and model for peers in establishing management rules and also offer theoretical and practical foundations for improving the management system of high-risk clinical research.

Objective:This study starts from the main problems existing in the current stage of the development of pediatric clinical research in China and focuses on the construction of a clinical research management system. By innovating the platform management model and enhancing personnel skills, we can provide support and assurance for improving the clinical research platform and its sustainable development in the future.Methods:This study established an integrated management platform for Industry-Sponsored Initiated Clinical Research Trial (IST) and Investigator Initiated Clinical Research (IIT) and implement integrated management of IST and IIT projects. At the same time, in response to the weak links in quality management, synchronous training of management and research talents should be implemented to achieve dual improvement in project management quality and platform service efficiency throughout the process.Results:We had optimized the clinical research organization structure, improved the management system, and strengthened the quality supervision of IIT projects by establishing rules and systems to improve the quality and efficiency of project management.Conclusions:Based on analyzing the current situation in China and referring to international experience, we have built a clinical research management platform in line with the development of the hospital, and implemented centralized management of the entire process of IST and IIT projects, strengthened project process quality control, which is expected to provide a reference for peers.

Objective:This study starts from the main problems existing in the current stage of the development of pediatric clinical research in China and focuses on the construction of a clinical research management system. By innovating the platform management model and enhancing personnel skills, we can provide support and assurance for improving the clinical research platform and its sustainable development in the future.Methods:This study established an integrated management platform for Industry-Sponsored Initiated Clinical Research Trial (IST) and Investigator Initiated Clinical Research (IIT) and implement integrated management of IST and IIT projects. At the same time, in response to the weak links in quality management, synchronous training of management and research talents should be implemented to achieve dual improvement in project management quality and platform service efficiency throughout the process.Results:We had optimized the clinical research organization structure, improved the management system, and strengthened the quality supervision of IIT projects by establishing rules and systems to improve the quality and efficiency of project management.Conclusions:Based on analyzing the current situation in China and referring to international experience, we have built a clinical research management platform in line with the development of the hospital, and implemented centralized management of the entire process of IST and IIT projects, strengthened project process quality control, which is expected to provide a reference for peers.

Objective:In response to the current situation where Investigator-Initiated Trial (IIT) management system of pediatric medical institutions in our country is inadequate and the management of high-risk projects needs to be strengthened, a pediatric hospital in Beijing has been selected as a pilot to develop a system and process suitable for IIT management. We aim to explore personalized management models for different types of research projects, especially high-risk ones, to improve the quality of pediatric IIT, reduce research risks, and enhance management efficiency.Methods:By analyzing the current management situation of high-risk pediatric IIT, optimization strategies were proposed to improve the internal IIT project management system and processes of the pilot unit, and effective management measures are promoted.Results:By revising the IIT project management system, improving the project application and approval processes, strengthening process quality control and personnel training, the risk control and quality supervision of such projects had been enhanced, thereby improving project quality and ensuring the rights and interests of research participants.Conclusions:After the pilot unit trialed a series of management measures for high-risk IIT projects, researchers' risk awareness has significantly increased, and project quality has been effectively improved. The Results provide a reference and model for peers in establishing management rules and also offer theoretical and practical foundations for improving the management system of high-risk clinical research.

Purpose: Investigation of stroke lesions mostly focuses on the grey matter (GM). White matter (WM) degeneration during acute stroke has remained understudied. In the present study, monkeys were employed to investigate the alterations in GM and WM in the brain following ischemic occlusion using diffusion tensor imaging (DTI). Materials and Methods: Permanent middle cerebral artery occlusion was induced in rhesus monkeys (n = 6) using an interventional approach. Serial DTI was conducted on a clinical 3 T in the hyperacute phase (2–6 hours), 48, and 96 hours post-occlusion. Regions of interest in GM and WM of lesion areas were selected for data analysis. Results: Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) in WM decreased substantially during hyperacute stroke, similar to those seen in GM. No obvious fractional anisotropy changes were seen in WM during the hyperacute phase until 48 hours poststroke when significant fiber loss was observed. Pseudo-normalization of MD, AD, and RD was seen at 96 hours. Pathological changes in WM and GM were observed in ischemic areas at 8, 48, and 96 hours poststroke. Relative changes in MD, AD, and RD of WM were correlated negatively with infarction volumes at 6 hours poststroke. Conclusion The present study revealed the microstructural changes in GM and WM of monkey brains during acute stroke using DTI. The preliminary results suggest that AD and RD may be sensitive surrogate markers to assess specific microstructural changes in WM during the hyperacute stroke.

Purpose: The corticospinal tract (CST) is a major tract for motor function. It can be impaired by stroke. Its degeneration is associated with stroke outcome. Diffusion tensor imaging (DTI) tractography plays an important role in assessing fiber bundle integrity. However, it is limited in detecting crossing fibers in the brain. The crossing fiber angular resolution of intra-voxel structure (CFARI) algorithm shows potential to resolve complex fibers in the brain. The objective of the present study was to improve delineation of CST pathways in monkey brains scanned by conventional DTI. Materials and Methods: Healthy rhesus monkeys were scanned by diffusion MRI with 128 diffusion encoding directions to evaluate the CFARI algorithm. Four monkeys with ischemic occlusion were also scanned with DTI (b = 1000 s/mm2, 30 diffusion directions) at 6, 48, and 96 hours poststroke. CST fibers were reconstructed with DTI and CFARI-based tractography and evaluated. A two-way repeated multivariate analysis of covariance was used to determine significances of changes in DTI indices, tract number, and volumes of the CST between hemispheres or poststroke time points. Results: CFARI algorithm revealed substantially more fibers originated from the ventral premotor cortex in healthy and stroke monkey brains than conventional DTI tractography. In addition, CFARI improved sensitivity in detecting CST abnormality compared to DTI tractography following stroke. Conclusion CFARI significantly improved delineation of the CST in the brain scanned by DTI with 30 gradient directions. It showed better sensitivity in detecting abnormity of the CST following stroke. Preliminary results suggest that CFARI could facilitate prediction of function outcomes after stroke.

Objective To evaluate the effect of dexmedetomidine on the tolerance to endotracheal tube, on agitation and other complications of patients undergoing transnasal transsphenoidal pituitary tumor resection.Methods One hundred and twenty-four patients aged 18-65 years, ASA physical status Ⅰ or Ⅱ) were randomly assigned to dexmedetomidine group (group D, n=60) and control group (group C, n=62).Group D were given intravenous infusion of dexmedetomidine during the operation and group C with saline.The extubation time, observation time in the post-anesthesia care unit (PACU), the incidence of emergence agitation, cough, postoperative sore throat and hoarseness were analyzed.Results The extubation time [(29.7±11.5) min vs (22.2±8.5) min] and the length of stay in PACU [(41.5±11.8) min vs (35.3±10.0) min] were significantly longer in group D than those in group C (P<0.05).There was no significant difference of the incidence of emergence agitation (26.3% vs 32.3%), cough (49.1% vs 53.2%), postoperative sore throat (14.0% vs 24.2%) and hoarseness (10.5% vs 19.4%) between two groups.Conclusion Intraoperative intravenous administration of dexmedetomidine can prolong the extubation time and the length of stay in PACU.The incidence of agitation, cough, postoperative sore throat and hoarseness was not affected by dexmedetomidine.

Objective In the present study,we use GC/MS-based metabolomics approaches to make analysis of serum metabolic profiles of healthy people and the hyperactivity of liver yang type of constitution in patients with essential hypertension.Try to establish the discriminant model,to discover biomarkers (group) of the hyperactivity of liver yang type of essential hypertension,and to explore the essential material basis of Traditional Chinese medicine syndrome theory.Methods Classified according to the guiding principles of Chinese medicine research,the hyperactivity of liver yang type of constitution in male patients with essential hypertension (n=18),as well as health volunteers (n=15) were randomly selected from Guang An Men Hospital clinic,wards and medical center in the first half of 2010,selected patients with essential hypertension requirements are not taking any drugs or Chinese herbs,or stop taking the various drugs more than one week.Extracted Venous Blood of subjects fasting for 12 hours,and serum was separated through centrifugation.Serum samples are stored and at-86℃ refrigerator.Survey and evaluate endogenous metabolism in serum samples of health control group and types of syndrome mentioned above by gas chromatograph mass spectrometry (GCMS)analysis.Then,analyze the metabolites with Partial Least Squares-Discriminant Analysis.Further use PCA to analyze the principal component factor loadings matrix analysis,and for variable scatter plot (Loading plot),significant increase or decrease the variables can be found from the figure.The combination of these variables is the lesion biomarkers group.Results Compared with the health control group,13 differentially expressed metabolites in the essential hypertension hyperactivity of liver yang type group can be identified (P＜0.05).8 metabolites were up-regulated expression:Uric acid,citrate,Octadecanoic acid,Hexadecanoic acid,Octadecadienoic acid,Leucine,Cholesterol,Norvaline,and 5 metabolites were down-regulated expression:arachidonate,Oleate,Alanine,Aspartic acid,glycine.Conclusion We are incline to regard that the 13 of EH patient serum differentially expressed metabolites are EH hyperactivity of liver yang syndrome metabolic biomarkers:Uric acid,citrate,Octadecanoic acid,Hexadecanoic acid,Octadecadienoic acid,Leucine,Cholesterol,Norvaline,Arachidonate,Oleate,Alanine,Aspartic acid,glycine.