Identification of Noncoding Functional Regulatory Variants of STIM1 Gene in Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH). METHODS: Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect STIM1 transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca2+ measurement were performed to study the mechanistic roles of those STIM1 noncoding variants in PAH. RESULTS: Five noncoding variants (rs3794050, rs7934581, rs3750996, rs1561876, and rs3750994) were identified and genotyped using Sanger sequencing. Rs3794050, rs7934581, and rs1561876 were associated with idiopathic PAH (recessive model, all P<0.05). Bioinformatics analysis showed that these 3 noncoding variants possibly affect the enhancer function of STIM1 or the microRNA (miRNA) binding to STIM1. Functional validation performed in HEK293 and pulmonary artery smooth muscle cells demonstrated that the noncoding variant rs1561876-G (STIM1 mutant) had significantly stronger transcriptional activity than the wild-type counterpart, rs1561876-A, by affecting the transcriptional regulatory function of both hsa-miRNA-3140-5p and hsa-miRNA-4766-5p. rs1561876-G enhanced intracellular Ca2+ signaling in human pulmonary artery smooth muscle cells secondary to calcium-sensing receptor activation and promoted proliferation of pulmonary artery smooth muscle cells under both normoxia and hypoxia conditions, suggesting a possible contribution to PAH development. CONCLUSIONS: The potential clinical implications of the 3 noncoding variants of STIM1, rs3794050, rs7934581, and rs1561876, are 2-fold, as they may help predict the risk and prognosis of idiopathic PAH and guide investigations on novel therapeutic pathway(s).

DCU-Net: Multi-scale U-Net for brain tumor segmentation.

BACKGROUND: Brain tumor segmentation plays an important role in assisting diagnosis of disease, treatment plan planning, and surgical navigation. OBJECTIVE: This study aims to improve the accuracy of tumor boundary segmentation using the multi-scale U-Net network. METHODS: In this study, a novel U-Net with dilated convolution (DCU-Net) structure is proposed for brain tumor segmentation based on the classic U-Net structure. First, the MR brain tumor images are pre-processed to alleviate the class imbalance problem by reducing the input of the background pixels. Then, the multi-scale spatial pyramid pooling is used to replace the max pooling at the end of the down-sampling path. It can expand the feature receptive field while maintaining image resolution. Finally, a dilated convolution residual block is combined to improve the skip connections in the training networks to improve the network's ability to recognize the tumor details. RESULTS: The proposed model has been evaluated using the Brain Tumor Segmentation (BRATS) 2018 Challenge training dataset and achieved the dice similarity coefficients (DSC) score of 0.91, 0.78 and 0.83 for whole tumor, core tumor and enhancing tumor segmentation, respectively. CONCLUSIONS: The experiment results indicate that the proposed model yields a promising performance in automated brain tumor segmentation.

P4VP Modified Zwitterionic Polymer for the Preparation of Antifouling Functionalized Surfaces.

Zwitterionic polymers are suitable for replacing poly(ethylene glycol) (PEG) polymers because of their better antifouling properties, but zwitterionic polymers have poor mechanical properties, strong water absorption, and their homopolymers should not be used directly. To solve these problems, a reversible-addition fragmentation chain transfer (RAFT) polymerization process was used to prepare copolymers comprised of zwitterionic side chains that were attached to an ITO glass substrate using spin-casting. The presence of 4-vinylpyridine (4VP) and zwitterion chains on these polymer-coated ITO surfaces was confirmed using 1H NMR, FTIR, and GPC analyses, with successful surface functionalization confirmed using water contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) studies. Changes in water contact angles and C/O ratios (XPS) analysis demonstrated that the functionalization of these polymers with ß-propiolactone resulted in hydrophilic mixed 4VP/zwitterionic polymers. Protein adsorption and cell attachment assays were used to optimize the ratio of the zwitterionic component to maximize the antifouling properties of the polymer brush surface. This work demonstrated that the antifouling surface coatings could be readily prepared using a "P4VP-modified" method, that is, the functionality of P4VP to modify the prepared zwitterionic polymer. We believe these materials are likely to be useful for the preparation of biomaterials for biosensing and diagnostic applications.

A Modified Inverted Nipple Correction Technique That Preserves Breastfeeding.

BACKGROUND: An inverted nipple may affect the appearance of the breasts and breastfeeding, but traditional surgical procedures might injure the normal lactiferous ducts and damage sensory functions. OBJECTIVES: The aim of the study was to propose a minimally invasive and reliable method that preserves breastfeeding and corrects grade I and II inverted nipples. METHODS: This was a randomized controlled trial of 230 female patients with unilateral or bilateral inverted nipples and 30 patients with normal nipples who visited the Preconception Counseling Department of our hospital from February 2009 to January 2016. The nipples in the distractor group underwent an operation with a distractor, while the control nipples were treated with daily exercises. The intervention lasted 6 months. The primary endpoint was full-term pregnancy breastfeeding for 4 months. The secondary endpoint was the completion of lactation without obvious complications, such as mastitis and nipple craze. RESULTS: Grade I and II nipples achieved increased height after the distractor was worn for 6 months and at 37 weeks of pregnancy (P < 0.05), while the control nipples achieved only a marginal improvement at 37 weeks of pregnancy. In the distractor group, the success rates were 84.9% and 79.3% for grade I and II nipples, respectively, compared with the control group (52.5% and 38.9%, respectively) (P < 0.05). After treatment with the distractor for 6 months, nipples in the distractor group showed no complications, such as skin numbness or nipple necrosis. CONCLUSIONS: The use of a distractor is a reliable and minimally invasive method for correcting grade I and II inverted nipples while preserving breastfeeding.

Modification of square face in men.

BACKGROUND: Women with elliptical faces are considered to be aesthetically appealing in Asia. Some men prefer this shape for themselves and choose to have their square-shaped face altered to an elliptical shape. To accomplish this, we perform an ostectomy that includes resection of the mandibular angle, splitting of the lateral cortex, and reduction in the width of the chin. METHODS: Nineteen men with a square face (aged 22-30 years) underwent ostectomy, including resection of the mandibular angle, splitting of the lateral cortex around the mandibular angle, and reduction of the width of the chin by an intraoral approach. RESULTS: The results of the ostectomy were satisfactory 3 to 6 months postoperatively. The bigonial distance was effectively reduced and stable chin contours were achieved. The overall shape of the face was elliptical. There was no microgenia, facial asymmetry, hematoma, infection, or permanent mental nerve injury. CONCLUSION: Ostectomy that includes resection of the mandibular angle, splitting of the lateral cortex, and reduction in the width of the chin is a safe and effective method to modify a man's square-shaped face into a more elliptical appearance.