Exosomes from adipose-derived stem cells activate sebocytes through the PI3K/AKT/SREBP-1 pathway to accelerate wound healing.

Sebocyte regeneration after injury is considered a key element of functional skin repair. Exosomes from adipose-derived stem cells (ADSCs-EXO) accelerate wound healing by promoting the proliferation of fibroblasts. However, the effects of ADSCs-EXO on sebocytes are largely unknown. In this study, the effects of ADSCs-EXO on sebocyte proliferation and migration were evaluated. The levels of phosphorylated AKT (p-AKT), AKT, sterol regulatory-element binding protein (SREBP), and perilipin-1 (PLIN-1) were detected with immunofluorescence, quantitative PCR, and western blot analysis. RNA-Seq was used to analyze the differential gene expression between the ADSCs-EXO group and the control group under anaerobic conditions. Lipogenesis was assessed with Nile red staining. In animal studies, full-thickness skin wounds in BALB/c mice were treated with gelatin methacrylate (GelMA) hydrogel-loaded sebocytes alone or in combination with ADSCs-EXO. Histopathological assessments of the wound tissues were performed Masson Trichrome staining, Immunohistochemical staining and so on. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway blocker LY294002 inhibited the effects of ADSCs-EXO on p-AKT and sebocytes proliferation. ADSCs-EXO also regulated the expression of SREBP-1 and PLIN-1 through the PI3K/AKT pathway in an oxygen level-dependent manner. In BALB/c mice, ADSCs-EXO accelerated sebocyte-assisted wound healing and regeneration. These in vitro and in vivo results supported that ADSCs-EXO can promote the regeneration of fully functional skin after injury through the PI3K/AKT-dependent activation of sebocytes.

Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy.

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.

Deep-Gamma: deep low-excitation fluorescence imaging global enhancement.

Lowering the excitation to reduce phototoxicity and photobleaching while numerically enhancing the fluorescence signal is a useful way to support long-term observation in fluorescence microscopy. However, invalid features, such as near-zero gradient dark backgrounds in fluorescence images, negatively affect the neural networks due to the network training locality. This problem makes it difficult for mature deep learning-based image enhancement methods to be directly extended to fluorescence imaging enhancement. To reduce the negative optimization effect, we previously designed Kindred-Nets in conjunction with a mixed fine-tuning scheme, but the mapping learned from the fine-tuning dataset may not fully apply to fluorescence images. In this work, we proposed a new, to the best of our knowledge, deep low-excitation fluorescence imaging global enhancement framework, named Deep-Gamma, that is completely different from our previously designed scheme. It contains GammaAtt, a self-attention module that calculates the attention weights from global features, thus avoiding negative optimization. Besides, in contrast to the classical self-attention module outputting multidimensional attention matrices, our proposed GammaAtt output, as multiple parameters, significantly reduces the optimization difficulty and thus supports easy convergence based on a small-scale fluorescence microscopy dataset. As proven by both simulations and experiments, Deep-Gamma can provide higher-quality fluorescence-enhanced images compared to other state-of-the-art methods. Deep-Gamma is envisioned as a future deep low-excitation fluorescence imaging enhancement modality with significant potential in medical imaging applications. This work is open source and available at https://github.com/ZhiboXiao/Deep-Gamma.

Deep SBP+: breaking through the space-bandwidth product limit based on a physical-driven cycle constraint framework.

To obtain an image with both high spatial resolution and a large field of view (FoV), we designed a deep space-bandwidth product (SBP)-expanded framework (Deep SBP+). Combining a single-captured low-spatial-resolution image with a large FoV and a few captured high-spatial-resolution images in sub-FoVs, an image with both high spatial resolution and a large FoV can be reconstructed via Deep SBP+. The physical model-driven Deep SBP+ reconstructs the convolution kernel as well as up-samples the low-spatial resolution image in a large FoV without relying on any external datasets. Compared to conventional methods relying on spatial and spectral scanning with complicated operations and systems, the proposed Deep SBP+ can reconstruct high-spatial-resolution and large-FoV images with much simpler operations and systems as well as faster speed. Since the designed Deep SBP+ breaks through the trade-off of high spatial resolution and large FoV, it is a promising tool for photography and microscopy.

sPhaseStation: a whole slide quantitative phase imaging system based on dual-view transport of intensity phase microscopy.

Whole slide imaging scans a microscope slide into a high-resolution digital image, and it paves the way from pathology to digital diagnostics. However, most of them rely on bright-field and fluorescence imaging with sample labels. In this work, we designed sPhaseStation, which is a dual-view transport of intensity phase microscopy-based whole slide quantitative phase imaging system for label-free samples. sPhaseStation relies on a compact microscopic system with two imaging recorders that can capture both under and over-focus images. Combined with the field of view (FoV) scan, a series of these defocus images in different FoVs can be captured and stitched into two FoV-extended under and over-focus ones, which are used for phase retrieval via solving the transport of intensity equation. Using a 10× micro-objective, sPhaseStation reaches the spatial resolution of 2.19 µm and obtains the phase with high accuracy. Additionally, it acquires a whole slide image of a 3m m×3m m region in 2 min. The reported sPhaseStation could be a prototype of the whole slide quantitative phase imaging device, which may provide a new perspective for digital pathology.

DARU-Net: A dual attention residual U-Net for uterine fibroids segmentation on MRI.

PURPOSE: Uterine fibroid is the most common benign tumor in female reproductive organs. In order to guide the treatment, it is crucial to detect the location, shape, and size of the tumor. This study proposed a deep learning approach based on attention mechanisms to segment uterine fibroids automatically on preoperative Magnetic Resonance (MR) images. METHODS: The proposed method is based on U-Net architecture and integrates two attention mechanisms: channel attention of squeeze-and-excitation (SE) blocks with residual connections, spatial attention of pyramid pooling module (PPM). We did the ablation study to verify the performance of these two attention mechanisms module and compared DARU-Net with other deep learning methods. All experiments were performed on a clinical dataset consisting of 150 cases collected from our hospital. Among them, 120 cases were used as the training set, and 30 cases are used as the test set. After preprocessing and data augmentation, we trained the network and tested it on the test dataset. We evaluated segmentation performance through the Dice similarity coefficient (DSC), precision, recall, and Jaccard index (JI). RESULTS: The average DSC, precision, recall, and JI of DARU-Net reached 0.8066 ± 0.0956, 0.8233 ± 0.1255, 0.7913 ± 0.1304, and 0.6743 ± 0.1317. Compared with U-Net and other deep learning methods, DARU-Net was more accurate and stable. CONCLUSION: This work proposed an optimized U-Net with channel and spatial attention mechanisms to segment uterine fibroids on preoperative MR images. Results showed that DARU-Net was able to accurately segment uterine fibroids from MR images.

Ultrathin Supratrochlear Artery Cutaneous Branch Flaps for Large Defects Around Eyebrows.

BACKGROUND: The key point of repairing large defects around eyebrows is to keep the eyebrow undistorted. The limited skin elevates the application difficulty of conventional methods such as direct suture or local flap. Forehead pedicle flaps do well in tension control. However, most of them are too thick for defects because the frontalis muscle must be included. Recently, 1 stable supratrochlear artery cutaneous branch was found, which provides an opportunity to make an ultrathin forehead flap with a good blood supply. This study aims to investigate whether the supratrochlear artery cutaneous branch flap could perform good esthetic reconstruction for defects around the eyebrow. METHODS: The authors retrospectively included 15 patients whose defect around the eyebrows was repaired by the supratrochlear artery cutaneous branch flap from June 2017 to June 2020. The authors followed up about their flap color and texture, scar, abnormal sensation, any complication, recurrence, and patient satisfaction for at least 6 months online or face-to-face. RESULTS: All of the flaps survived, without distortion of the eyebrows or inner canthi. Similar flap color, texture, and thickness with the nearby skin were obtained, except 2 patients reported pigmentation. Donor and receptor scars were acceptable. There was no recurrence or other complications. All of the patients were satisfied with the surgery effect. CONCLUSIONS: The supratrochlear artery cutaneous branch flap is a valuable alternative method to repair large defects around the eyebrows. It can avoid facial distortion and achieve good esthetic outcomes in single-stage surgery.

The value of HPV genotypes combined with clinical indicators in the classification of cervical squamous cell carcinoma and adenocarcinoma.

BACKGROUND: To investigate the differences in HPV genotypes and clinical indicators between cervical squamous cell carcinoma and adenocarcinoma and to identify independent predictors for differentiating cervical squamous cell carcinoma and adenocarcinoma. METHODS: A total of 319 patients with cervical cancer, including 238 patients with squamous cell carcinoma and 81 patients with adenocarcinoma, were retrospectively analysed. The clinical characteristics and laboratory indicators, including HPV genotypes, SCCAg, CA125, CA19-9, CYFRA 21-1 and parity, were analysed by univariate and multivariate analyses, and a classification model for cervical squamous cell carcinoma and adenocarcinoma was established. The model was validated in 96 patients with cervical cancer. RESULTS: There were significant differences in SCCAg, CA125, CA19-9, CYFRA 21-1, HPV genotypes and clinical symptoms between cervical squamous cell carcinoma and adenocarcinoma (P < 0.05). Logistic regression analysis showed that SCCAg and HPV genotypes (high risk) were independent predictors for differentiating cervical squamous cell carcinoma from adenocarcinoma. The AUC value of the established classification model was 0.854 (95% CI: 0.804-0.904). The accuracy, sensitivity and specificity of the model were 0.846, 0.691 and 0.899, respectively. The classification accuracy was 0.823 when the model was verified. CONCLUSION: The histological type of cervical cancer patients with persistent infection of high-risk HPV subtypes and low serum SCCAg levels was more prone to being adenocarcinoma. When the above independent predictors occur, the occurrence and development of cervical adenocarcinoma should be anticipated, and early active intervention treatment should be used to improve the prognosis and survival of patients.

Combining multiparametric MRI features-based transfer learning and clinical parameters: application of machine learning for the differentiation of uterine sarcomas from atypical leiomyomas.

OBJECTIVES: To explore the feasibility and effectiveness of machine learning (ML) based on multiparametric magnetic resonance imaging (mp-MRI) features extracted from transfer learning combined with clinical parameters to differentiate uterine sarcomas from atypical leiomyomas (ALMs). METHODS: The data of 86 uterine sarcomas between July 2011 and December 2019 and 86 ALMs between June 2013 and June 2017 were retrospectively reviewed. We extracted deep-learning features and radiomics features from T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI). The two feature extraction methods, transfer learning and radiomics, were compared. Random forest was adopted as the classifier. T2WI features, DWI features, combined T2WI and DWI (mp-MRI) features, and combined clinical parameters and mp-MRI features were applied to establish T2, DWI, T2-DWI, and complex multiparameter (mp) models, respectively. Predictive performance was assessed with the area under the receiver operating characteristic curve (AUC). RESULTS: In the test set, the T2, DWI, T2-DWI and complex mp models based on transfer learning (AUCs range from 0.76 to 0.81, 0.80 to 0.88, 0.85 to 0.92, and 0.94 to 0.96, respectively) outperformed the models based on radiomics (AUCs of 0.73, 0.76, 0.79, and 0.92, respectively). Moreover, the complex mp model showed the best prediction performance, with the Resnet50-complex mp model achieving the highest AUC (0.96) and accuracy (0.87). CONCLUSIONS: Transfer learning is feasible and superior to radiomics in the differential diagnosis of uterine sarcomas and ALMs in our dataset. ML models based on deep learning features of nonenhanced mp-MRI and clinical parameters can achieve good diagnostic efficacy. KEY POINTS: • The ML model combining nonenhanced mp-MRI features and clinical parameters can distinguish uterine sarcomas from ALMs. • Transfer learning can be applied to differentiate uterine sarcomas from ALMs and outperform radiomics. • The most accurate prediction model was Resnet50-based transfer learning, built with the deep-learning features of mp-MRI and clinical parameters.

Factors influencing magnetic resonance imaging finding of endopelvic fascial edema after ultrasound-guided high-intensity focused ultrasound ablation of uterine fibroids.

OBJECTIVE: Investigate the relationships between endopelvic fascial edema and its influencing factors after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids. METHODS: This retrospective study included 688 women with uterine fibroids treated by USgHIFU; based on post-treatment MRI, the patients were divided into two groups: endopelvic fascial edema group and nonedema group. The specific location of fascial edema of each patient was also recorded. Fascial edema and fibroid features and treatment parameters were set as the dependent and independent variables, respectively, and the correlations were studied using univariate and multivariate analyses. The relationship between the pain-related adverse events and location of fascial edema was analyzed by χ2 and fisher's exact tests. RESULTS: Edema and nonedema groups had 556 and 112 patients, respectively. Among the edema patients, posterior fascial edema incidence was the highest. Multifactorial analysis showed that the energy efficiency factor (EEF), fibroid location, and enhancement type were positively associated with endopelvic fascial edema (p < 0.05), while the distance from dorsal surface of the fibroid to sacrum was negatively correlated (p < 0.001). Patients with anterior, posterior and perirectal, and right lateral fascial edemas were associated with lower abdominal pain, sacrococcygeal pain, and leg numbness/pain, respectively. CONCLUSION: Post-USgHIFU ablation, patients were prone to developing endopelvic fascial edema, and some of them experienced pain-related adverse events. The fibroid location, its types of contrast enhancement, the distance from the dorsal surface of the fibroid to the sacrum, and EEF were the influencing factors resulting in the endopelvic fascial edema after USgHIFU ablation.

Patellar shape is associated with femoral trochlear morphology in individuals with mature skeletal development.

BACKGROUND: As several studies have detected correlations between patellar and femoral trochlear development, this raises the question of whether patellar shape is associated with trochlear developmental outcomes. METHODS: Patellar shape and femoral trochlear morphology were retrospectively analyzed in 183 subjects, of whom 61 each were classified as having Wiberg type I, II, and III patellae (groups A, B, and C, respectively). The sulcus angle (SA), lateral trochlea inclination angle (LTA), medial trochlear inclination angle (MTA), lateral facet length (LFL), medial facet length (MFL), lateral trochlear height (LTH), medial trochlear height (MTH), trochlea sulcus height (TH), and lateral-medial trochlear facet distance (TD) were analyzed as a means of evaluating trochlear morphology. Trochlear depth, trochlear condyle asymmetry, and trochlear facet asymmetry were additionally calculated, and differences in trochlear morphology and correlations between trochlear morphology and patellar shape were evaluated. RESULTS: The femoral trochlear parameters of patients in group A differed significantly from those of patients in groups B and C. No significant differences between groups B and C were evident. Patellar shape was positively correlated with LTA, MTA, MFL, trochlear condyle asymmetry, and trochlear facet asymmetry, and was negatively correlated with SA. CONCLUSIONS: These data indicated that patellar shape and trochlear morphology are related to one another,which suggest normalized patella morphology surgery and trochlear surgery are better choices for patients with patella instability. TRIAL REGISTRATION: Retrospectively registered.

The safety and ablation efficacy of ultrasound-guided high-intensity focused ultrasound ablation for desmoid tumors.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs). METHOD: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure. RESULTS: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment. CONCLUSION: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.

Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways.

Refractory diabetic wounds can cause persistent inflammation and delayed healing due to hypoxia. Currently, no optimal solution is available. Exosomes of adipose stem cells (ADSCs-exo) may promote skin wound healing, however, molecular mechanisms remains mysterious. We found significantly enhanced survival and proliferation of adipose stem cells after hypoxia induction compared to normoxia. Here, we aimed to investigate if hypoxic adipose stem cells exosomes (HypADSCs-exo) participate in hypoxia adaptability and accelerate diabetic wound healing. Based on high-throughput sequencing, 215 microRNAs (miRNAs) were upregulated and 369 miRNAs downregulated in HypADSCs-exo compared to ADSCs-exo. Up-regulated miR-21-3p, miR-126-5p, miR-31-5p whereas down-regulated gene miR-99b and miR-146-a correlated with wound healing. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), miRNAs might regulate cell metabolism, differentiation and Transforming growth factor-ß (TGF-ß) function. Consistently, HpyADSCs-exo could promote diabetic wounds healing and inhibit inflammation through PI3K/AKT signaling pathway. Collectively, HpyADSCs-exo can promote diabetic wound healing as an alternative strategy to improve wound healing.

Gluteal Augmentation with Fat Grafting: Literature Review.

BACKGROUND: The buttock is the second sex feature of the human body, and the graceful buttock curve gives people confidence. Although the safety of gluteal augmentation with autologous fat grafting is still controversial, the proportion of operations is increasing year by year. PURPOSE: To provid a comprehensive and detailed review of the literature on gluteal augmentation with fat grafting. METHODS: A comprehensive review of the published literature through September of 2020 was performed in PubMed database, with the search terms "gluteal augmentation," "buttock augmentation," "Brazilian buttock lift," "fat grafting," "fat transfer," "gluteal AND aesthetic," "gluteal AND anatomy." RESULTS: A total of 64 articles were included. On the basis of the information obtained, surgical recommendations are proposed to achieve buttocks as close as possible to aesthetic standard and improve surgical safety. CONCLUSION: With a good grasp of the anatomical structure of the buttocks, complications can be reduced. At the same time, based on the theoretical basis of buttock aesthetics, better postoperative results can be obtained. LEVEL OF EVIDENCE III: 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 .

[The Value of MRI in Early Cervical Cancer Staging with Vaginal Filling of Ultrasound Gel].

OBJECTIVE: To investigate the value of MRI after ultrasonic gel vagina filling in the staging of early-stage cervical cancer. METHODS: A total of 158 patients with cervical cancer who underwent MRI examination after their cervical cancer diagnosis was confirmed by cervical biopsy were prospectively enrolled. Routine MRI examination was performed first, followed by another MRI examination after vaginal filling with ultrasound gel. Two physicians used a double-blind method to determine the staging of cervical cancer based on the MRI images before and after vaginal filling of ultrasound gel. Results of the postoperative pathology analysis were used as the golden standard. The positive predictive value and negative predictive value for stage Ⅱa cases of the two examinations of the same patient were compared, and the sensitivity, specificity and accuracy in identifying stage Ⅱa cervical cancer were compared. RESULTS: Two physicians used the double blind method to determine the staging of cervical cancer based on conventional MRI images, achieving moderate consistency ( κ=0.680). However, for the staging of cervical cancer with MRI images after vaginal filling of ultrasound gel, the two physicians achieved highly consistent results ( κ=0.932). Regarding identifying stage Ⅱa cervical cancer, the positive predictive value of conventional MRI was 66.67%, the negative predictive value was 76.74%, and the sensitivity, specificity and accuracy were 70.59%, 73.33% and 72.15%, respectively. The positive predictive value of MRI after vaginal filling of ultrasound gel was 90.91%, the negative predictive value was 91.3%, and the sensitivity, specificity and accuracy were 88.24%, 93.33% and 91.14%, respectively. The sensitivity, specificity and accuracy of the two methods were compared and the difference was statistical significant ( P<0.05). CONCLUSION: MRI examination after ultrasound gel vaginal filling has better diagnostic value for identifying stage Ⅱa cervical cancer. The method is simple and easy to do, and can be used in routine MRI examination of cervical cancer.

MRI evaluation of endopelvic fascial swelling and analysis of influencing factors in patients with uterine fibroids after high-intensity focused ultrasound ablation.

Purpose: To evaluate endopelvic fascial swelling in patients with uterine fibroids after high-intensity focused ultrasound (HIFU) ablation on magnetic resonance imaging (MRI) and investigate the factors that influence endopelvic fascial swelling.Methods: MRI and clinical data from 188 patients with uterine fibroids who were treated with HIFU were analyzed retrospectively. The patients were divided into a fascial swelling group and a non-swelling group, and the degree of swelling was graded. Fascial swelling was set as the dependent variable, and factors such as baseline characteristics and HIFU parameters, were set as the independent variables. The relationship between these variables and fascial swelling was analyzed by univariate and multivariate analyses. Correlations between the factors and the degree of fascial swelling were evaluated by Kruskal-Wallis test.Results: The univariate analysis revealed that the fibroid location, distance from the fibroid to the sacrum, sonication time, treatment time, treatment intensity, therapeutic dose (TD), and energy efficiency (EEF) all affected the endopelvic fascial swelling (p < 0.05). Subsequently, multivariate analysis showed that the distance from the fibroid to the sacrum was significantly correlated with fascial swelling (p < 0.05). Moreover, TD and sonication time were significantly positively correlated with the degree of fascial swelling (p < 0.05). The incidence of sacrococcygeal pain was significantly correlated with fascial swelling (p < 0.05).Conclusion: The distance from the fibroid to the sacrum was a protective factor for fascial swelling. TD and sonication time were significantly positively correlated with the degree of fascial swelling.

Reasons for different therapeutic effects of high-intensity focused ultrasound ablation on excised uterine fibroids with different signal intensities on T2-weighted MRI: a study of histopathological characteristics.

OBJECTIVE: The objective of this study was to explore the correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of excised uterine fibroids with different signal intensities as visualized on T2-weighted magnetic resonance imaging (MRI). METHODS: We collected 47 specimens of uterine fibroids after surgical resection and classified them into four groups according to preoperative T2-weighted MRI hypo-intense, isointense, heterogeneous intense and homogeneous hyper-intense. Then, specimens in each group were irradiated by HIFU with the same parameters and the necrotic tissue volume was calculated. The smooth muscle cell (SMC) count and collagen fiber content were quantitatively measured and compared between different groups. We analyzed the correlation between the necrotic tissue volume and SMC count and the collagen fiber content. RESULTS: Necrotic tissue volume gradually decreased from the hypo-intense group to the homogeneous hyper-intense group (p = .008). The SMC count from the hypo-intense group to the homogeneous hyper-intense group was 215.6 ± 59.3, 237.0(89.5), 232.3 ± 72.5 and 330.5 ± 30.9, respectively; collagen fiber content was 0.65 ± 0.07, 0.64 ± 0.10, 0.53 ± 0.11 and 0.41 ± 0.06, respectively. Comparison among the four groups showed that SMC count progressively increased (p = .001) but collagen fiber content progressively decreased (p = .000) from the hypo-intense group to the homogeneous hyper-intense group. Correlation analysis showed that necrotic tissue volume was negatively correlated with SMC count (R = -0.488, p=.013) but positively correlated with collagen fiber content (R = 0.534, p = .005). CONCLUSIONS: Differences in histopathological characteristics may be one of the reasons for different therapeutic effects of HIFU ablation on uterine fibroids with different signal intensities on T2-weighted MRI.

Methylation-Mediated Silencing of MicroRNA-211 Decreases the Sensitivity of Melanoma Cells to Cisplatin.

BACKGROUND Malignant melanoma is recalcitrant to most existing chemotherapies, and aberrant expression of miR-211 plays prominent roles in progression of melanoma. However, the trigger mechanism of aberrant miR-211 expression in melanoma is still elusive. MATERIAL AND METHODS We used qRT-PCR to test miR-211 expression. Cell viability assay and mouse xenograft assay were performed to examine the role of miR-211 on the sensitivity of melanoma cells to cisplatin. The epigenetic modification of miR-211 promoter was assess by DNA methylation analysis and DAC treatment. RESULTS In this study, decreased miR-211 expression was detected. Bisulfite sequencing PCR showed that DNA hypermethylation contributed to the downregulation of miR-211 in melanoma tissues. In melanoma cells, overexpressed 211 could enhance the anticancer effect of cisplatin and restoration of miR-211 rendered susceptibility to cisplatin in cisplatin-resistant cells. And the same result was showed in vivo by mouse xenograft assay. What is more, DAC treatment could increase miR-211 expression and EZH2 expression was increased in cisplatin-resistant cells. MiR-211 could be transcriptionally repressed by EZH2 mediated promoter methylation. CONCLUSIONS Taken together, our findings revealed that epigenetic modification of miR-211 governed melanoma cell chemosensitivity and were involved in the progression of tumorigenesis.

Uterine Peristalsis Before and After Ultrasound-Guided High-Intensify Focused Ultrasound (USgHIFU) Treatment for Symptomatic Uterine Fibroids.

BACKGROUND This study investigated uterine peristalsis before and after ultrasound-guided high-intensify focused ultrasound (USgHIFU) treatment for symptomatic uterine fibroids by cine magnetic resonance imaging (cine MRI). MATERIAL AND METHODS A total of 30 patients with symptomatic uterine fibroids were treated by USgHIFU, who were subjected to cine MRI before and after USgHIFU treatment in the periovulatory phase. The images were analyzed for the existence, direction, and frequency of uterine peristalsis. The effects of uterine volume, the largest fibroid volume and location, and the fibroid number were examined before and after USgHIFU treatment. RESULTS The incidence of uterine peristalsis was significantly increased after USgHIFU treatment. The main direction of uterine peristalsis before and after USgHIFU was cervix-to-fundus. In 12 cases, uterine peristalsis newly emerged after USgHIFU, and the largest fibroid volumes in these 12 cases were significantly smaller than in the remaining 18 cases before and after USgHIFU. The reduction rates of the largest fibroid volume in the 12 cases were significantly higher than in the remaining 18 cases. The largest fibroids were mainly located in the intramural area before and after USgHIFU. CONCLUSIONS USgHIFU treatment may contribute to the recovery of uterine peristalsis in patients with symptomatic fibroids, as detected by cine MRI. Uterine peristalsis recovery was related to the largest fibroid volume, especially for intramural fibroids.

MiR-21 regulates the apoptosis of keloid fibroblasts by caspase-8 and the mitochondria-mediated apoptotic signaling pathway via targeting FasL.

MicroRNA-21 (miR-21) has been found to be upregulated in keloid tissue and to affect the proliferation and apoptosis of keloid fibroblasts; however, the possible mechanisms remain unclear. In this study, we aimed to evaluate the role of miR-21 in FasL-induced caspase-8 activation and the mitochondria-mediated apoptotic signaling pathway in keloid fibroblasts. Our study found that the protein level of FasL was decreased by miR-21 over-expression, while being enhanced by miR-21 inhibition in keloid fibroblasts. Subsequently, the mitochondria-mediated apoptosis of keloid fibroblasts was restrained by miR-21 over-expression, as evidenced by enhanced mitochondrial membrane potential and decreased production of mitochondrial ROS. Moreover, over-expression of miR-21 inhibited the activation of the caspase-8 and the mitochondria-mediated apoptotic signaling pathway. As expected, inhibition of miR-21 had the opposite effects. Finally, silencing of FasL suppressed miR-21 inhibition-induced apoptosis by inactivation of caspase-8 and the mitochondria-mediated apoptotic signaling pathway, which was comparable to Z-IETD-FMK, a caspase-8 inhibitor. Taken together, these results suggest that miR-21 regulates the apoptosis of keloid fibroblasts via targeting FasL, and caspase-8 and the mitochondria-mediated apoptotic signaling pathway is involved in this process. Our findings provide evidence that miR-21 may be considered to be a therapeutic target for keloids.