The Distribution of Transplanted Umbilical Cord Mesenchymal Stem Cells in Large Blood Vessel of Experimental Design With Traumatic Brain Injury.

The authors aim to track the distribution of human umbilical cord mesenchymal stem cells (MSCs) in large blood vessel of traumatic brain injury -rats through immunohistochemical method and small animal imaging system. After green fluorescent protein (GFP) gene was transfected into 293T cell, virus was packaged and MSCs were transfected. Mesenchymal stem cells containing GFP were transplanted into brain ventricle of rats when the infection rate reaches 95%. The immunohistochemical and small animal imaging system was used to detect the distribution of MSCs in large blood vessels of rats. Mesenchymal stem cells could be observed in large vessels with positive GFP expression 10 days after transplantation, while control groups (normal group and traumatic brain injury group) have negative GFP expression. The vascular endothelial growth factor in transplantation group was higher than that in control groups. The in vivo imaging showed obvious distribution of MSCs in the blood vessels of rats, while no MSCs could be seen in control groups. The intravascular migration and homing of MSCs could be seen in rats received MSCs transplantation, and new angiogenesis could be seen in MSCs-transplanted blood vessels.

Feasibility evaluation of kilovoltage cone-beam computed tomography dose calculation following scatter correction: investigations of phantom and representative tumor sites.

BACKGROUND: To study the feasibility of kilovoltage cone-beam computed tomography (KV-CBCT) dose calculation following scatter correction. METHODS: CIRS 062 and Catphan 504 phantoms were used in this study, and 40 randomly selected subjects representing a variety of cases (ten head cancer cases, ten chest cancer cases, ten abdominal cancer cases and ten pelvic cavity cancer cases) were enrolled. We developed in-house software called the cone-beam CT imaging toolkit (CITK) to improve the quality of CBCT images. We first aligned each planning computed tomography (pCT) image with the corresponding CBCT image using rigid registration after scatter correction. Hounsfield unit-relative electron density (HU-RED) calibration was applied to the CBCT images. The pCT plan was then recalculated on CBCT images. Finally, the dosimetric differences between the two plans were evaluated. The dosimetric parameters included the D98, D2, Dmean, conformity index (CI), homogeneity index (HI) and other organ at risk (OAR) dose parameters of the planning target volume (PTV). The dose distribution index (DDI) and the gamma index were also assessed. Paired Student's t-tests or Wilcoxon rank tests were used to evaluate differences. P<0.05 was considered significant. RESULTS: In the phantom and patient cases, the average dosimetric difference was less than 1% in the PTV and OARs. There was no significant difference in the CI or HI between the two plans. The gamma pass rate of 2%/2 mm was greater than 95% in both plans. There was a significant difference in the DDI between the two plans in the chest group but not in the other groups. CONCLUSIONS: The results suggest that CBCT has high accuracy in dose calculation via scatter correction and HU-RED calibration.

Bioinformatics analysis of Myelin Transcription Factor 1.

BACKGROUND AND OBJECTIVE: We aimed to further study the role of Myelin Transcription Factor 1(MyT1) in tumor and other diseases and epigenetic regulation, and better understand the regulatory mechanism of MyT1. METHODS: Using bioinformatics analysis, the structure and function of MyT1sequence were predicted and analyzed using bioinformatics analysis, and providing a theoretical basis for further experimental verification and understanding the regulatory mechanism of MyT1. The first, second and third-level structures of MyT1 were predicted and analyzed by bioinformatics analysis tools. RESULTS: MyT1 is found to be an unstable hydrophilic protein, rather than a secretory protein, with no signal peptide or trans-membrane domain; total amino acids located on the surface of the cell membrane. It contains seven zinc finger domains structurally. At sub-cellular level, MyT1 is localized in the nucleus. The phosphorylation site mainly exists in serine, and its secondary structure is mainly composed of random coils and alpha helices; the three-dimensional structure is analyzed by modeling. CONCLUSIONS: In this study, the structure and function of MyT1 protein were predicted, thereby providing a basis for subsequent expression analysis and functional research; it laid the foundation for further investigation of the molecular mechanism involved in the development of diseases.

Synergy between Clinical Microenvironment Targeted Nanoplatform and Near-Infrared Light Irradiation for Managing Pseudomonas aeruginosa Infections.

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.

Geometric accuracy evaluation of a six-degree-of-freedom (6-DoF) couch with cone beam computed tomography (CBCT) using a phantom and correlation study of the position errors in pelvic tumor radiotherapy.

BACKGROUND: To assess the position accuracy of the six-degree-of-freedom (6-DoF) couch based on cone beam computed tomography (CBCT) and exploit the correlation of the six degrees errors. METHODS: CT scans of an anthropomorphic phantom and patients were obtained at 3 mm slice thicknesses using a Philips scanner at the head, first supine and prostrate positions. An Eclipse Treatment Planning System was used to create a treatment plan. Different levels of known position errors were introduced to simulate patient position status for the anthropomorphic phantom. CBCT datasets for each position were acquired and registered to original CT datasets to evaluate the accuracy of the 6-DoF couch and determine the setup errors of patients. The setup errors of 200 CBCT datasets from 14 patients with pelvic tumors were analyzed. The correlations between six degrees position errors were finally extracted. RESULTS: For the phantom study, the difference between known introduced errors and the setup errors were almost negligible. The deviation (mean ± one standard deviation) in registration methods were (0.01±0.02) cm, (0.04±0.075) cm, (0.02±0.004) cm, (0.01±0.04)°, (0.1±0.08)°, (0.03±0.05)° and (0.01±0.01) cm, (0.03±0.007) cm, (0.01±0.01) cm, (0.05±0.06)°, (0.08±0.08)°, (0.04±0.05)° for supine and prone position, respectively. The deviation in positions were (0.07±0.10) cm, (0.16±0.02) cm, (0.08±0.06) cm, (0.54±0.46)°, (0.24±0.16)°, (0.09±0.09)° and (0.06±0.09) cm, (0.19±0.09) cm, (0.09±0.07) cm, (0.49±0.49)°, (0.16±0.08)°, (0.1±0.13)° for bone and soft tissue registration methods, respectively. For patient data, the setup errors were (-0.07±0.22) cm, (0.14±0.35) cm, (-0.12±0.4) cm, (0.79±1.6)°, (0.41±0.71)°, (-0.03±0.8)° for supine position and (0.16±0.27) cm, (0.19±0.48) cm, (-0.05±0.34) cm, (1.1±1.49)°, (0.65±1.00)°, (-0.23±0.75)° for prone position, respectively. There is a significant moderate correlation between the longitudinal and pitch directions and between the vertical and pitch directions when the patient is in the supine position. CONCLUSIONS: The six-dimensional couch positioning verification system based on CBCT has high accuracy and can meet the requirements of precise radiotherapy for pelvic tumors. There is a certain correlation between translation direction and rotation direction.

A Bioadhesive Nanoplatform Enhances the Permeation of Drugs Used to Treat Diabetic Macular Edema.

The management of diabetic macular edema (DME), a condition that leads to an irreversible and severe visual impairment, remains a substantial challenge worldwide. In this study, we developed a bioadhesive nanoplatform with enhanced drug penetration to explore alternative treatment modalities for DME. This nanoparticulate formulation consisted of a sequence of an amphiphilic phenylboronic acid-based block and random glycopolymer with a high loading capacity for dexamethasone (DEX) of up to 20% and sustained drug release in vitro at a clinically relevant dose. The bioadhesive nanocarriers penetrated the sclera and choroid and were distributed in the retina under the action of phenylboronic acid to further promote drug permeation and retention in target lesions. The pathological analysis, electroretinography examination and immunofluorescence staining revealed that the nanoformulation of DEX much more markedly reduced the symptoms of and inflammation associated with DME than the drug alone, without affecting the function of the retina. Bioadhesive drug delivery systems are expected to be a feasible approach to treat DME and other fundus diseases.

A bio-inspired injectable hydrogel as a cell platform for real-time glycaemic regulation.

Frequent subcutaneous insulin injection and islet transplantation are promising therapeutic options for type 1 diabetes mellitus. However, poor patient compliance, insufficient appropriate islet ß cell donors and body immune rejection limit their clinical applications. The design of a platform capable of encapsulating insulin-secreting cells and achieving real-time blood glucose regulation, is a so far unmet need. Herein, inspired by the natural processes of regulating blood glucose in pancreatic islet ß cells, we developed a poly(N-isopropylacrylamide-co-dextran-maleic acid-co-3-acrylamidophenylboronic acid) (P(AAPBA-Dex-NIPAM)) hydrogel as a cell platform with glucose responsiveness and thermo-responsiveness for the therapy of diabetes. This platform showed good biocompatibility against insulin-secreting cells and presented glucose-dependent insulin release behaviour. The bioinspired P(AAPBA6-Dex-NIPAM64) hydrogel had a positive effect on real-time glycaemic regulation, as observed by intraperitoneal glucose tolerance tests. The non-fasting blood glucose of diabetic rats was restored to a normal level during the period of treatment. Additionally, the inflammatory response did not occur after administration of the platform. Collectively, we expected that the bio-mimetic platform combined with an insulin-secreting capability could be a new diabetic treatment strategy.

Characterization of microvessels and parenchyma in in-line phase contrast imaging CT: healthy liver, cirrhosis and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis, and approximately 80% of HCC cases develop from cirrhosis. Imaging techniques in the clinic seem to be insufficient for revealing the microstructures of liver disease. In recent years, phase contrast imaging CT (PCI-CT) has opened new avenues for biomedical applications owing to its unprecedented spatial and contrast resolution. The aim of this study was to present three-dimensional (3D) visualization of human healthy liver, cirrhosis and HCC using a PCI-CT technique called in-line phase contrast imaging CT (ILPCI-CT) and to quantitatively evaluate the variations of these tissues, focusing on the liver parenchyma and microvasculature. METHODS: Tissue samples from 9 surgical specimens of normal liver (n=3), cirrhotic liver (n=2), and HCC (n=4) were imaged using ILPCI-CT at the Shanghai Synchrotron Radiation Facility (SSRF) without contrast agents. 3D visualization of all ex vivo liver samples are presented. To quantitatively evaluate the vessel features, the vessel branch angles of each sample were clearly depicted. Additionally, radiomic features of the liver parenchyma extracted from the 3D images were measured. To evaluate the stability of the features, the percent coefficient of variation (%COV) was calculated for each radiomic feature. A %COV <30 was considered to be low variation. Finally, one-way ANOVA, followed by Tukey's test, was used to determine significant changes among the different liver specimens. RESULTS: ILPCI-CT allows for a clearer view of the architecture of the vessels and reveals more structural details than does conventional radiography. Combined with the 3D visualization technique, ILPCI-CT enables the acquisition of an accurate description of the 3D vessel morphology in liver samples. Qualitative descriptions and quantitative assessment of microvessels demonstrated clear differences among human healthy liver, cirrhotic liver and HCC. In total, 38 (approximately 51%) radiomic features had low variation, including 11 first-order features, 16 GLCM features, 6 GLRLM features and 5 GLSZM features. The differences in the mean vessel branch angles and 3 radiomic features (first-order entropy, GLCM-inverse variance and GLCM-sum entropy) were statistically significant among the three groups of samples. CONCLUSIONS: ILPCI-CT may allow for morphologic descriptions and quantitative evaluation of vessel microstructures and parenchyma in human healthy liver, cirrhotic liver and HCC. Vessel branch angles and radiomic features extracted from liver parenchyma images can be used to distinguish the three kinds of liver tissues.

Plan quality and robustness in field junction region for craniospinal irradiation with VMAT.

PURPOSE: To propose a "staggered overlap" technique in volumetric modulated arc therapy (VMAT) for craniospinal irradiation (CSI) and compare the dose distribution and plan robustness with "overlap" technique and "gradient optimization" approach. METHODS AND MATERIALS: 6 patients previously treated in our clinic were retrospectively selected. 9 VMAT plans of each patient were optimized with "staggered overlap", "overlap" and "gradient optimization" in overlapping region of 3 cm, 6 cm, and 9 cm separately. For the "staggered overlap" plan, adjacent field sets were intentionally overlapped by staggering field edges in an appropriate step size to avoid sharp dose gradient. Evaluation metrics including V95%, D2%, D98%, conformity number (CN) and homogeneity index (HI) were employed to evaluate the dose distribution. Moreover, shifts of the upper spinal field isocenter in each direction were performed to simulate junction errors for robustness analysis. RESULTS: The CN and HI of VMAT plans with "staggered overlap" were 0.82 (0.811-0.822) and 0.113 (0.112-0.114), while they were 0.778 (0.776-0.782) and 0.131 (0.130-0.131) for plans with "gradient optimization". In the robustness study, <3% dose deviations were found for 5 mm shifts in lateral and vertical directions with all techniques. In cranial-caudal direction, "overlap" technique created hot spots (D2% > 170%) and cold spots (D98% < 44%) in the junction region with 10 mm shifts. The dose deviations were decreased to 22% for plans with "staggered overlap" and 9 cm overlapping region. CONCLUSION: "Staggered overlap" technique provides better plan quality as compared to "gradient optimization" approach and makes the plan more robust against junction errors as compared to "overlap" technique.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy.

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy.