Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches.

Crohn's disease (CD) is a recurrent, chronic inflammatory condition of the gastrointestinal tract which is a clinical subtype of inflammatory bowel disease for which timely and non-invasive diagnosis in children remains a challenge. A novel predictive risk signature for pediatric CD diagnosis was constructed from bioinformatics analysis of six mRNAs, adenomatosis polyposis downregulated 1 (APCDD1), complement component 1r, mitogen-activated protein kinase kinase kinase kinase 5 (MAP3K5), lysophosphatidylcholine acyltransferase 1, sphingomyelin synthase 1 and transmembrane protein 184B, and validated using samples. Statistical evaluation was performed by support vector machine learning, weighted gene co-expression network analysis, differentially expressed genes and pathological assessment. Hematoxylin-eosin staining and immunohistochemistry results showed that APCDD1 was highly expressed in pediatric CD tissues. Evaluation by decision curve analysis and area under the curve indicated good predictive efficacy. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis confirmed the involvement of immune and cytokine signaling pathways. A predictive risk signature for pediatric CD is presented which represents a non-invasive supplementary tool for pediatric CD diagnosis.

Quantitative assessment of inframammary fold in Asians: an MRI study.

Background: The inframammary fold (IMF) is a critical structure affecting the aesthetics of the breast, yet the anatomy and location of the IMF remain controversial. The purpose of this study was to quantitatively evaluate the thickness and location of IMF utilizing magnetic resonance imaging (MRI). Methods: The MRI images of 240 breasts from 120 Asian women were analyzed. The quantitative measurements consisted of breast width, breast projection, nipple to inframammary fold, breast volume, IMF tissue thickness, and IMF position. The IMF position was evaluated by referring to the ribs, as well as measuring the distance between IMF and the inferior of the fifth rib. Results: The mean values of central thickness, medial thickness, and lateral thickness were 1.50±0.59, 1.46±0.60, and 1.76±1.04 cm, respectively. IMF central thickness demonstrated a moderate positive correlation with breast projection (r=0.559, P<0.001) and breast volume (r=0.523, P<0.001). The proportions of IMF located at the fourth intercostal, the fifth rib, the fifth intercostal, the sixth rib and the sixth intercostal were 5.8%, 29.2%, 43.3%, 20.4% and 1.3%, respectively. The average distance between IMF and the inferior of the fifth rib was 0.69±1.40 cm. 60.0% of women had near-symmetrical IMF, while 17.5% had left higher IMF and 22.5% had right higher IMF. Conclusions: This study used MRI to quantitatively assess the anatomy of IMF. The detailed knowledge of IMF would facilitate the ideal aesthetic outcome of mammaplasty.

Reciprocal REGγ-Nrf2 Regulation Promotes Long Period ROS Scavenging in Oxidative Stress-Induced Cell Aging.

Increased accumulation of reactive oxygen species (ROS) and decline of adaptive response of antioxidants to oxidative stimuli has been implicated in the aging process. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation is a core event in attenuating oxidative stress-associated aging. The activity is modulated by a more complex regulatory network. In this study, we demonstrate the proteasome activator REGγ function as a new regulator of Nrf2 activity upon oxidative stress in cell aging model induced by hydrogen peroxide (H2O2). REGγ deficiency promotes cell senescence in primary MEF cells after H2O2 treatment. Accordingly, ROS scavenging is accelerated in WT cells but blunted in REGγ lacking cells during 12-hour recovery from a 1-hour H2O2 treatment, indicating long-lasting antioxidant buffering capacity of REGγ. Mechanistically, through GSK-3ß inhibition, REGγ enhances the nuclear distribution and transcriptional activity of Nrf2, which is surveyed by induction of phase II enzymes including Ho1 and Nqo1. Meanwhile, Nrf2 mediates the transcriptional activation of REGγ upon H2O2 stimulation. More interestingly, short-term exposure to H2O2 leads to transiently upregulation and gradually descent of REGγ transcription, however sustained higher REGγ protein level even in the absence of H2O2 for 24 hours. Thus, our results establish a positive feedback loop between REGγ and Nrf2 and a new layer of adaptive response after oxidative stimulation that is the REGγ-GSK-3ß-Nrf2 pathway.

Modulation of Osteogenesis and Angiogenesis Activities Based on Ionic Release from Zn-Mg Alloys.

The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg2+ and Zn2+ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn-xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn2+ and Mg2+ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg2+ while decreasing the Zn2+ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn-0.5Mg and Zn-1Mg due to the higher concentration of Mg2+. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn2+ release (6.415 µg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn2+ concentration. Although the concentration of Zn ion was decreased in Zn-0.5Mg and Zn-1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg2+ and Zn2+ in Zn-Mg alloys show a dual modulation effect. The Zn-0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn-Mg composition in designs for orthopedic application.

MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis.

BACKGROUND: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.

REGγ drives Lgr5+ stem cells to potentiate radiation induced intestinal regeneration.

Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a marker of intestinal stem cells (ISCs), is considered to play key roles in tissue homoeostasis and regeneration after acute radiation injury. However, the activation of Lgr5 by integrated signaling pathways upon radiation remains poorly understood. Here, we show that irradiation of mice with whole-body depletion or conditional ablation of REGγ in Lgr5+ stem cell impairs proliferation of intestinal crypts, delaying regeneration of intestine epithelial cells. Mechanistically, REGγ enhances transcriptional activation of Lgr5 via the potentiation of both Wnt and Hippo signal pathways. TEAD4 alone or cooperates with TCF4, a transcription factor mediating Wnt signaling, to enhance the expression of Lgr5. Silencing TEAD4 drastically attenuated ß-catenin/TCF4 dependent expression of Lgr5. Together, our study reveals how REGγ controls Lgr5 expression and expansion of Lgr5+ stem cells in the regeneration of intestinal epithelial cells. Thus, REGγ proteasome appears to be a potential therapeutic target for radiation-induced gastrointestinal disorders.

Identification and Validation of m6A-Related lncRNA Signature as Potential Predictive Biomarkers in Breast Cancer.

The metastasis and poor prognosis are still regarded as the main challenge in the clinical treatment of breast cancer (BC). Both N6-methyladenosine (m6A) modification and lncRNAs play vital roles in the carcinogenesis and evolvement of BC. Considering the unknown association of m6A and lncRNAs in BC, this study therefore aims to discern m6A-related lncRNAs and explore their prognostic value in BC patients. Firstly, a total of 6 m6A-related lncRNAs were screened from TCGA database and accordingly constructed a prognostic-predicting model. The BC patients were then divided into high-risk and low-risk groups dependent on the median cutoff of risk score based on this model. Then, the predictive value of this model was validated by the analyses of cox regression, Kaplan-Meier curve, ROC curve, and the biological differences in the two groups were validated by PCA, KEGG, GSEA, immune status as well as in vitro assay. Finally, we accordingly constructed a risk prognostic model based on the 6 identified m6A-related lncRNAs, including Z68871.1, AL122010.1, OTUD6B-AS1, AC090948.3, AL138724.1, EGOT. Interestingly, the BC patients were divided into the low-risk and high-risk groups with different prognoses according to the risk score. Notably, the risk score of the model was an excellent independent prognostic factor. In the clinical sample validation, m6A regulatory proteins were differentially expressed in patients with different risks, and the markers of tumor-associated macrophages and m6A regulators were co-localized in high-risk BC tissues. This well-validated risk assessment tool based on the repertoire of these m6A-related genes and m6A-related lncRNAs, is of highly prognosis-predicting ability, and might provide a supplemental screening method for precisely judging BC prognosis.

Twin Boundary Superstructures Assembled by Periodic Segregation of Solute Atoms.

Twinning is a common deformation mechanism in metals, and twin boundary (TB) segregation of impurities/solutes plays an important role in the performances of alloys such as thermostability, mobility, and even strengthening. The occurrence of such segregation phenomena is generally believed as a one-layer coverage of solutes alternately distributed at extension/compression sites, in an orderly, continuous manner. However, in the Mn-free and Mn-containing Mg-Nd model systems, we reported unexpected three- and five-layered discontinuous segregation patterns of the coherent {101̅1} TBs, and not all the extension sites occupied by solutes larger in size than Mg, and even some larger sized solutes taking the compression sites. Nd/Mn solutes selectively segregate at substitutional sites and thus to generate two new types of ordered two-dimensional TB superstructures or complexions. These findings refresh the understanding of solute segregation in the perfect coherent TBs and provide a meaningful theoretical guidance for designing materials via targeted TB segregation.

Identification of pyroptosis-related lncRNAs for constructing a prognostic model and their correlation with immune infiltration in breast cancer.

The inflammasome-dependent cell death, which is denoted as pyroptosis, might be abnormally regulated during oncogenesis and tumour progression. Long non-coding RNAs (LncRNAs) are pivotal orchestrators in breast cancer (BC), which have the potential to be a biomarker for BC diagnosis and therapy. The present study aims to explore the correlation between pyroptosis-related lncRNAs and BC prognosis. In this study, a profile of 8 differentially expressed lncRNAs was screened in the TCGA database and used to construct a prognostic model. The BC patients were divided into high- and low-risk groups dependent on the median cutoff of the risk score in the model. Interestingly, the risk model significantly distinguished the clinical characteristics of BC patients between high- and low-risk groups. Then, the risk score of the model was identified to be an excellent independent prognostic factor. Notably, the GO, KEGG, GSEA and ssGSEA analyses revealed the different immune statuses between the high- and low-risk groups. Particularly, the 8 lncRNAs expressed differentially in BC tissues between two risk subgroups in vitro validation. Collectively, this constructed well-validated model is of high effectiveness to predict the prognosis of BC, which will provide novel means that is applicable for BC prognosis recognition.

Two-Dimensional Frank-Kasper Z Phase with One Unit-Cell Thickness.

Z phase is one of the three basic units by which the Frank-Kasper (F-K) phases are generally assembled. Compared to the other two basic units, that is, A15 and C15 structures, the Z structure is rarely experimentally observed because of a relatively large volume ratio among the constituents to inhibit its formation. Moreover, the discovered Z structures are generally the three-dimensional ordered Gibbs bulk phases to conform to their thermodynamic stability. Here, we confirmed the existence of a metastable two-dimensional F-K Z phase that has only one unit-cell height in the crystallography in a model Mg-Sm-Zn system, using atomic-scale scanning transmission electron microscopy combined with the first-principles calculations. Self-adapted atomic shuffling can convert the simple hexagonal close-packed structure to the topologically close-packed F-K Z phase. This finding provides new insight into understanding the formation mechanism and clustering behavior of the F-K phases and even quasicrystals in general condensed matters.

The Use of DCE-MRI to Evaluate the Blood Supply to the Nipple-Areola Complex: A Study in 245 Asian Women.

BACKGROUND: Understanding the main blood supply to the nipple-areola complex (NAC) is important for breast plastic surgery. However, previous reports have involved studies of cadavers and small sample sizes. OBJECTIVES: This study aimed to identify and classify the in vivo blood supply to the NAC based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: DCE-MRI images of 393 breasts in 245 Asian women obtained from March 2012 to October 2019 were included retrospectively. Axial, coronal, and sagittal maximum-intensity projection images were evaluated to identify all vessels supplying the NAC. Blood supply to the NAC was classified into 9 anatomic zones: superomedial (Ia), medial (Ib), inferomedial (Ic), superolateral (IIa), lateral (IIb), inferolateral (IIc), central (III), inferior (IV), and superior (V). RESULTS: A total of 637 source vessels were identified in 393 breasts. Of the 393 breasts, 211 (53.7%) were supplied by a single zone, 132 (33.6%) by 2 zones, 38 (9.7%) by 3 zones, and 12 (3.1%) by 4 zones. Of the 637 vessels, 269 (42.2%) vessels were in zone Ia, 180 (28.3%) vessels were in zone IIa, and <10% of vessels were in the other zones. The number of NAC perfusion zones (P = 0.093) and the distribution of source vessels (P = 0.602) did not differ significantly between the left and right breasts. CONCLUSIONS: DCE-MRI provides a clear indication of the blood supply to the NAC. Blood vessels from the superomedial and superolateral zones were the predominant sources of blood supplying the NAC.

Nonsymmetrical Segregation of Solutes in Periodic Misfit Dislocations Separated Tilt Grain Boundaries.

Interfacial segregation is ubiquitous in mulit-component polycrystalline materials and plays a decisive role in material properties. So far, the discovered solute segregation patterns at special high-symmetry interfaces are usually located at the boundary lines or are distributed symmetrically at the boundaries. Here, in a model Mg-Nd-Mn alloy, we confirm that elastic strain minimization facilitated nonsymmetrical segregation of solutes in four types of linear tilt grain boundaries (TGBs) to generate ordered interfacial superstructures. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy observations indicate that the solutes selectively segregate at substitutional sites at the linear TGBs separated by periodic misfit dislocations to form such two-dimensional planar structures. These findings are totally different from the classical McLean-type segregation which has assumed the monolayer or submonolayer coverage of a grain boundary and refresh understanding on strain-driven interface segregation behaviors.

Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway.

Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids.

3D images of the silicone implants in capsular contracture after breast augmentation using magnetic resonance imaging with SPACE sequence.

BACKGROUND: Capsular contracture is a common complication after breast augmentation. However, no objective methods are available to assess capsular contracture at present. The goal of the present study was to evaluate the correlation between capsular contracture and 3D images of the silicone implants by using magnetic resonance imaging (MRI) with sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) sequence. METHODS: Twenty-one patients (42 breasts) underwent breast augmentation, had postoperative MRI examinations with SPACE sequence, and the evaluation of the Baker grade by two trained plastic surgeons. Capsular thickness was measured on the T2-weighted images. The software ITK-SNAP was used to reconstruct 3D images of the implants. The fold characteristics such as number, depth, direction, and distribution were compared with the Baker grade. RESULTS: Of the 42 breasts, 14, 8, 12, and 8 breasts were classified as Baker grade I, II, III, and IV, respectively. The MRI images of breasts with Baker grade III or IV revealed a thicker capsule (mean of 2.29 mm) as compared to the capsule with the lower Baker grades (mean of 1.58 mm). The 3D images of implants showed no difference in the number of folds between the groups with different Baker grades. The fold direction and fold distribution differed between grade I to II and grade III to IV. CONCLUSION: The 3D image of an implant with pathological folds is a potential and feasible diagnostic indication of capsular contracture. LEVEL OF EVIDENCE: IV.

Current Progress in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon type of T-cell lymphoma. Although with a low incidence, the epidemiological data raised the biosafety and health concerns of breast reconstruction and breast augmentation for BIA-ALCL. Emerging evidence confirms that genetic features, bacterial contamination, chronic inflammation, and textured breast implant are the relevant factors leading to the development of BIA-ALCL. Almost all reported cases with a medical history involve breast implants with a textured surface, which reflects the role of implant surface characteristics in BIA-ALCL. With this review, we expect to highlight the most significant features on etiology, pathogenesis, diagnosis, and therapy of BIA-ALCL, as well as we review the physical characteristics of breast implants and their potential pathogenic effect and hopefully provide a foundation for optimal choice of type of implant with minimal morbidity.

Downregulation of Epac Reduces Fibrosis and Induces Apoptosis Through Akt Signaling in Human Keloid Fibroblasts.

BACKGROUND: A keloid is a type of pathological scar often caused by abnormal tissue repair after a skin injury and is more common in genetically susceptible individuals. cAMP is a universal second messenger and regulates critical physiological processes, including calcium homeostasis, secretion, cell fate, and gene transcription, by affecting the expression of the exchange protein directly activated by cAMP (Epac). Epac has two isoforms, Epac1 (cAMP-GEF-1) and Epac2 (cAMP-GEF-II), which show varying expression levels depending on the tissue and cell type. The expression of Epac1 in keloids has not yet been investigated. MATERIALS AND METHODS: Keloid tissue and normal dermal skin tissue were analyzed by hematoxylin and eosin staining and immunofluorescence. Primary human keloid fibroblasts (HKFs) and human normal dermal fibroblasts were studied using immunofluorescence, wound healing tests, reverse transcription polymerase chain reaction, and western blot analysis with different concentrations of the Epac1 inhibitor ESI-09. RESULTS: Downregulation of Epac was performed using ESI-09, a specific Epac inhibitor. The proliferation and migration capacities of HKFs and human normal dermal fibroblasts showed an ESI-09 concentration-dependent decrease. Furthermore, the apoptosis rates were significantly different between fibroblasts treated with ESI-09 and control fibroblasts. In addition, the phosphorylation level of Akt was significantly decreased, indicating that ESI-09 reduces fibrosis and induces apoptosis through Akt signaling in HKFs. CONCLUSIONS: Our results illustrate the role of Epac1 in regulating fibroblast function during keloid pathogenesis and indicate that Epac1 may be a potential therapeutic target in keloid treatment.

Knockout of E2F1 Inhibits Adipose Stem Cell Proliferation and Differentiation in Fat Transplantation by Repressing Peroxisome Proliferator-Activated Receptor Gamma Expression.

Adipose-derived stem cells (ADSCs) possess pluripotent differentiation potential and self-replication ability, which is highly significant in the field of tissue engineering. Cell-assisted lipotransfer (CAL) with ADSCs benefits fat survival. In this study, we focus on the effect of transcription factor E2F1 during CAL. The wild-type (WT) ADSCs were mixed with WT adipocytes, and the E2F1-/- ADSCs were mixed with E2F1-/- adipocytes. Then 2 cell mixtures were inoculated on the back 2 sides of E2F1-/- mice, respectively denoted as the WT group (WT ADSCs + WT adipose cells) and E2F1-/- group (E2F1-/- ADSCs + E2F1-/- adipose cells). At week 4, the fat graft was heavier in the WT group, with less necrotic area, more survival of mature adipocytes, and more proliferating ADSCs, compared with the E2F1-/- group. More capillaries were transformed from ADSCs in the WT group than in the E2F1-/- group. The in vitro protein levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) were higher in WT ADSCs than in E2F1-/- ADSCs. Therefore, these findings suggest that knockout of E2F1 could affect ADSCs to inhibit the survival of fat grafts by downregulating PPAR-γ expression.

Imaging of the Silicone Implant with a 3D SPACE MR Sequence: The Accuracy for Estimating Implant Volume and Reconstructing Implant Deformation in Breast Surgery.

OBJECTIVE: The study is to assess the accuracy and reliability of 3D simulated magnetic resonance imaging with SPACE sequence for estimating implant volume and reconstructing implant deformation, which may assist in the diagnosis of implant complications and making individualized surgical plans for these patients. METHODS: MRI examinations of ten silicone implants were performed with T2, H2O-excitation SPACE sequence (T2-spc-H2O) and silicone-excitation SPACE sequence (T2-spc-Silicone) to find the most accurate method to estimate implant volume by ITK-SNAP. The effect of implant deformation and voxel size of silicone-excitation SPACE sequence on volume measurement was investigated. Thirteen normal patients and ten patients with implant complications (Wuhan Tongji Hospital from March 2017 to May 2019) were enrolled for testing the accuracy and reliability of 3D simulated MRI with silicone-excitation SPACE sequences for volume measurement and reconstructing implant deformation in patients. RESULTS: The absolute volume differences of T2-spc-Silicone group were significantly less than T2-spc-H2O and T2 group (6.28 vs. 23.27 vs. 42.19 mL, P < 0.05) in vitro. No significant difference was found between the normality group and the deformation group for estimating the volume of implants. Besides, the voxel size of T2-spc-Silicone from 0.5 × 0.5 × 0.5 mm to 5.0 × 5.0 × 5.0 mm did not significantly affect the accuracy of volume measurement of the implants in deformation state. However, 3D images of the implant became blurred with the voxel size increased. With the voxel size larger than 1.5 × 1.5 × 1.5 mm, the scores of image quality decreased significantly. The number of folds could not be identified accurately with the voxel size larger than 2.0 × 2.0 × 2.0 mm. In normal patients, the measurement errors of T2-spc-Silicone were around 10 mL. In the patients with implant complications, there was no significant difference between measured volume and the actual volume of implants. Moreover, implant deformations were clearly presented by T2-spc-Silicone with the voxel size of 1.0 × 1.0 × 1.0 mm. The results showed excellent intraobserver reliability (ICC = 0.997 > 0.8), and internal consistency ranged from 0.986 to 0.997 (P < 0.001). CONCLUSIONS: The method to measure implant volume by 3D simulated magnetic resonance imaging with T2-spc-Silicone sequence had possessed desirable accuracy and reliability. The deformation of the implant and the voxel size of the T2-spc-Silicone sequence didn't exhibit a significant effect on the accuracy of the measurement. T2-spc-Silicone with voxel size less than 2.0 × 2.0 × 2.0 mm could be used for 3D reconstruction of the implant deformation. The 1.0 × 1.0 × 1.0 mm was a suitable voxel size to reconstruct implant deformation clearly and quickly. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identifying miRNA modules associated with progression of keloids through weighted gene co-expression network analysis and experimental validation in vitro.

Keloid is a type of skin fibroproliferative disease, characterized by excessive deposition of collagen in the extracellular matrix, myofibroblast activation and invasive growth to the surrounding normal skin tissue. However, the specific pathogenesis of keloids is not yet fully understood and existing treatment strategies are unsatisfied. It is therefore urgent to explore new biomarkers associated with its progression for keloids. In this study, the microarray dataset GSE113620 was downloaded from the Gene Expression Omnibus (GEO) database to screen out the differential expression of miRNAs (DEMs). The DEMs with large variance were applied to construct a weighted gene co-expression network to identify miRNA modules that are closely relevant to keloid progression. It is worth noting that miR-424-3p in the blue module (r = 0.98, p = 1e-18) is considered to be the ultimate target most relevant to keloid progression through co-expressed network analysis. Subsequently, the results of molecular biology experiments determine that miR-424-3p targeting Smad7 significantly enhanced the ability of cell proliferation, migration and collagen secretion after transfection with miR-424-3p mimic, while the apoptosis rate was significantly reduced. On the contrary, the miR-424-3p inhibitor performs the exact opposite function.