Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model

<p>Abstract</p> <p>Background</p> <p>Inflammatory responses are detected in the retina of patients with age-related macular degeneration and <it>Ccl2^-/-/Cx3cr1^-/-</it>mice on rd8 background,(<it>Ccl2^-/-/Cx3cr1^-/-</it>mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of <it>Ccl2^-/-/Cx3cr1^-/-</it>mice.</p> <p>Methods</p> <p>Recombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old C<it>cl2^-/-/Cx3cr1^-/-</it>mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.</p> <p>Results</p> <p>The continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that <it>IL-17a </it>was substantially decreased after the treatment. Expression of <it>TNF-α </it>showed a similar pattern to <it>IL-17a</it>. The results were consistent in duplicated arrays and confirmed by qRT-PCR.</p> <p>Conclusions</p> <p>We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in <it>Ccl2^-/-/Cx3cr1^-/-</it>mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.</p

The assessment and application of form evaluation algorithms in coordinate metrology

Three-dimensional coordinate measurements present a range of new challenges to measurement instruments and to the numerical algorithms, which significantly determine the performance of the measurements. Advanced measurement techniques provide a means of obtaining the data points that are accurately representative of the inspected surfaces. Numerical form evaluation algorithms characterize geometric dimensions and verify the conformance to a given tolerance from the 3D measurement data, which is linked the design process and dimension inspection. This thesis addresses mainly the form evaluation algorithms.Generally, two types Qf algorithms are employed in the form evaluation software of coordinate measurements: the least squares methods and the Mini-max methods. Other methods, such as minimum average deviation method, error curve analysis methods have also been proposed and employed. Different algorithms are based on different mathematical principles and may provide different form evaluation parameters on the same data set. This inconsistency is a significant issue and is a focus of current research. This thesis examines the present controversy to help users to select and employ appropriate form evaluation algorithms.For these purposes, taking spheres as an example, a set of criteria has been drawn up for comparing the existing form evaluation algorithms and selecting a proper algorithm for a specific measurement case. The criteria aim to control and minimize the influence of the measurement error, form errors and the evaluation algorithms on the inspection results. Based on these criteria, appropriate procedures for comparison and selection of the algorithms, such as computer simulation and experimental methods have been developed. General recommendations for the use of these algorithms have been given.From the conclusions of comparison and selection of the algorithms, it is found that the non-linear least square method (NLS) can derive a random measurement uncertainty on the estimated radius of a sphere which is independent of the form error of the measured spheres. Therefore, the random error propagation model of the estimated radius derived by the NLS method has been formulated, which can be used to provide a measurement uncertainty for any single measurement and applied to predict the random errors of a CMM. Also, by analysing the estimated parameters of the calibrated sphere, such as the deviation of the estimated radius, sphericity and residual error, the squareness errors of a CMM has been modelled mathematically and predicted.The criteria for judging the algorithms are concerned with the accuracy indices of the estimated geometric parameters. For any algorithm, it is assumed that data points are reasonably accurate and representative of the geometric elements concerned. To obtain a reliable assessment of geometric form, data pre-processing is necessary. In this thesis, an approach of data pre-processing by operating on the data according to the functional requirements of nominally spherical objects has been introduced and applied. Taking eroded electrical contacts as examples, an approach to pre-processing data, referred to as the Defect Removal Method, is proposed and developed

CT Image Changes of Severe Acute Pancreatitis Based on Smart Electronic Medical Augmented Reality in Nursing Practice

Severe acute pancreatitis (SAP) is traditionally treated with chemical analysis. Faced with the increasing maturity of CT imaging technology, it is necessary to use more advantageous CT imaging to treat SAP. In this article, 72 SAP patients admitted to the Affiliated Hospital of Southwest Medical University were selected for study, of which 62 were severely ill, 8 were exacerbated, and 2 changed from severe to mild. This article combines the patient’s case records and related CT images during treatment from the perspective of nursing and conducts nursing research on the application of CT image changes in severe acute pancreatitis in nursing practice. CT image processing uses CT imaging system workstation (DICOM). The results of the study showed that, in the care of patients, 21 cases had recurrence after internal drainage, and the cure rate was 91.1%. Internal drainage is an effective way to treat SAP. The higher the incidence of pancreatitis, the more likely it is to relapse after SAP internal drainage, which may be related to repeated episodes of pancreatitis and repeated inflammation of the pancreas and pancreatic duct damage. 4 of the relapsed cases in this article are postchronic pancreatitis SAP, and the relapsed cases account for 50% of the chronic pancreatic cases. This may be due to chronic fibrosis of the branched and main pancreatic ducts, continuous abnormal pancreatic juice drainage. Therefore, it is necessary to further explore the prognosis of different causes of SAP. In terms of complication care, the overall complication rate was 16.6%. One patient died of postoperative hemorrhage. Analysis of the causes of cyst recurrence and complications may be closely related to the mechanism of the occurrence and development of SAP. The initiating factor of SAP is that the pancreatic tissue is damaged due to inflammation, trauma, or microcirculation disorder, and then the pancreatic juice leaks out of the pancreas, wrapping the pancreatic juice; it takes a certain time for the capsule of fibrous knot tissue to form and strengthen

Pathogenic gene screening in 91 Chinese patients with short stature of unknown etiology with a targeted next-generation sequencing panel

Abstract Background Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening. Methods Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed. Results The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia. Conclusions Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management