CircFOXO3 mediates hypoxia-induced autophagy of endometrial stromal cells in endometriosis.

Endometriosis is a benign gynecological disease that shares some common features of malignancy. Autophagy plays vital roles in endometriosis and influences endometrial cell metastasis, and hypoxia was identified as the initiator of this pathological process through hypoxia inducible factor 1 alpha (HIF-1α). A newly discovered circular RNA FOXO3 (circFOXO3) is critical in cell autophagy, migration, and invasion of various diseases and is reported to be related to hypoxia, although its role in endometriosis remains to be elucidated up to now. In this study, a lower circFOXO3 expression in ectopic endometrium was investigated. Furthermore, we verified that circFOXO3 could regulate autophagy by downregulating the level of p53 protein to mediate the migration and invasion of human endometrial stromal cells (T HESCs). Additionally, the effects of HIF-1α on circFOXO3 and autophagy were examined in T HESCs. Notably, overexpression of HIF-1α could induce autophagy and inhibit circFOXO3 expression, whereas overexpressing of circFOXO3 under hypoxia significantly inhibited hypoxia-induced autophagy. Mechanistically, the direct combination between HIF-1α and HIF-1α-binding site on adenosine deaminase 1 acting on RNA (ADAR1) promoter increased the level of ADAR1 protein, which bind directly with circFOXO3 pre-mRNA to block the cyclization of circFOXO3. All these results support that hypoxia-mediated ADAR1 elevation inhibited the expression of circFOXO3, and then autophagy was induced upon loss of circFOXO3 via inhibition of p53 degradation, participating in the development of endometriosis.

Transcriptome-wide N6-methyladenosine (m6A) methylation profiling of long non-coding RNAs in ovarian endometriosis.

N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.

Automated diagnosis of schizophrenia based on spatial-temporal residual graph convolutional network.

BACKGROUND: Schizophrenia (SZ), a psychiatric disorder for which there is no precise diagnosis, has had a serious impact on the quality of human life and social activities for many years. Therefore, an advanced approach for accurate treatment is required. NEW METHOD: In this study, we provide a classification approach for SZ patients based on a spatial-temporal residual graph convolutional neural network (STRGCN). The model primarily collects spatial frequency features and temporal frequency features by spatial graph convolution and single-channel temporal convolution, respectively, and blends them both for the classification learning, in contrast to traditional approaches that only evaluate temporal frequency information in EEG and disregard spatial frequency features across brain regions. RESULTS: We conducted extensive experiments on the publicly available dataset Zenodo and our own collected dataset. The classification accuracy of the two datasets on our proposed method reached 96.32% and 85.44%, respectively. In the experiment, the dataset using delta has the best classification performance in the sub-bands. COMPARISON WITH EXISTING METHODS: Other methods mainly rely on deep learning models dominated by convolutional neural networks and long and short time memory networks, lacking exploration of the functional connections between channels. In contrast, the present method can treat the EEG signal as a graph and integrate and analyze the temporal frequency and spatial frequency features in the EEG signal. CONCLUSION: We provide an approach to not only performs better than other classic machine learning and deep learning algorithms on the dataset we used in diagnosing schizophrenia, but also understand the effects of schizophrenia on brain network features.

The diagnosis and treatment of pediatric clinical myocarditis in China: a multicenter retrospective study.

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.

Blood Eosinophil Count and Its Determinants in a Chinese Population-Based Cohort.

INTRODUCTION: Blood eosinophil count has been shown markedly variable across different populations. However, its distribution in Chinese general population remains unclear. We aimed to investigate blood eosinophil count and its determinants in a Chinese general population. METHODS: In this population-based study, general citizens of Sichuan province in China were extracted from the China Pulmonary Health study. Data on demographics, personal and family history, living condition, lifestyle, spirometry, and complete blood count test were obtained and analyzed. A stepwise multivariate binary logistic regression analysis was performed to identify determinants of high blood eosinophils (>75th percentile). RESULTS: A total of 3,310 participants were included, with a mean age (standard deviation) of 47.0 (15.6) years. In total population, the median blood eosinophil count was 110.0 (interquartile range [IQR]: 67.2-192.9) cells/µL, lower than that in smokers (133.4 cells/µL, IQR: 79.3-228.4) and patients with asthma (140.7 cells/µL, IQR: 79.6-218.2) or post-bronchodilator airflow limitation (141.5 cells/µL, IQR: 82.6-230.1), with a right-skewed distribution. Multivariate analyses revealed that oldness (aged ≥60 years) (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.11-2.48), smoking ≥20 pack-years (OR: 1.90, 95% CI: 1.20-3.00), raising a dog/cat (OR: 1.72, 95% CI: 1.17-2.52), and occupational exposure to dust, allergen, and harmful gas (OR: 1.58, 95% CI: 1.15-2.15) were significantly associated with high blood eosinophils. CONCLUSION: This study identifies a median blood eosinophil count of 110.0 cells/µL and determinants of high blood eosinophils in a Chinese general population, including oldness (aged ≥60 years), smoking ≥20 pack-years, raising a dog/cat, and occupational exposure to dust, allergen, and harmful gas.

Differential expression profiles and functional prediction of circular RNAs in lung cancer patients with chronic obstructive pulmonary disease: a pilot study.

Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.

A novel mechanism regulating pyroptosis-induced fibrosis in endometriosis via lnc-MALAT1/miR-141-3p/NLRP3 pathway†.

Endometriosis is a chronic inflammatory disease distinguished by ectopic endometrium and fibrosis. NLRP3 inflammasome and pyroptosis are present in endometriosis. Aberrant increase of Long noncoding (Lnc)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a vital role in endometriosis. However, the relationship between lnc-MALAT1, pyroptosis, and fibrosis is not completely known. In the present study, we found that the pyroptosis levels in ectopic endometrium of patients with endometriosis were significantly increased, consistent with fibrosis levels. Lipopolysaccharide (LPS) + ATP could induce pyroptosis of primary endometrial stromal cells (ESCs), thereby releasing interleukin (IL)-1ß and stimulating transforming growth factor (TGF)-ß1-mediated fibrosis. NLRP3 inhibitor MCC950 had the same effect as TGF-ß1 inhibitor SB-431542 in suppressing the fibrosis-inducing effect of LPS + ATP in vivo and in vitro. The abnormal increase of lnc-MALAT1 in ectopic endometrium was connected with NLRP3-mediated pyroptosis and fibrosis. Leveraging bioinformatic prediction and luciferase assays combined with western blotting and quantitative reverse transcriptase-polymerase chain reaction, we validated that lnc-MALAT1 sponges miR-141-3p to promote NLRP3 expression. Silencing lnc-MALAT1 in HESCs ameliorated NLRP3-mediated pyroptosis and IL-1ß release, thereby relieving TGF-ß1-mediated fibrosis. Consequently, our findings suggest that lnc-MALAT1 is critical for NLRP3-induced pyroptosis and fibrosis in endometriosis through sponging miR-141-3p, which may indicate a new therapeutic target of endometriosis treatment.

METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility.

BACKGROUND: Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation. METHODS: We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A. RESULTS: The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein. CONCLUSIONS: METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.

Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial.

RESEARCH QUESTION: Is sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)? DESIGN: This open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3-7 (n = 87) or 2.5 mg letrozole on cycle days 3-7 with a sequential injection of 75 IU HMG on cycle days 8-10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle. RESULTS: Women receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events. CONCLUSIONS: The data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.

Low dose of liraglutide combined with metformin leads to a significant weight loss in Chinese Han women with polycystic ovary syndrome: a retrospective study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with complex pathophysiological mechanism. It is reported that even a modest weight loss of 5-10% substantially may improve the reproductive and metabolic profile. This study aims to assess the efficacy of the low dose of liraglutide (0.6 mg QD) combined with metformin (0.85 mg BID) in weight loss in Chinese Han women with PCOS. METHODS: We included clinical data of 102 obese/overweight (≥18 years, body mass index ≥28 kg/m2 or ≥24 kg/m2) women who were diagnosed with PCOS from October 2016 to March 2018 in Wuhan Union Hospital initially. They were treated with dinae-35, low dose of liraglutide (0.6 mg QD) and metformin (0.85 mg BID) for 12 weeks. The demographic and clinical data were retrieved retrospectively, and weight loss was the main outcome measure. Student's paired t-test and Wilcoxon rank sum test were used to compare the differences before and after therapy, p < 0.05 was considered statistically significant. RESULTS: Participants(n = 102)had lost a mean of 7.20 ± 3.42 kg of body weight (95%CI: 6.55-7.86, p < 0.001), and the mean reduction of BMI was 2.87 ± 1.36 kg/m2 (95%CI: 0.02-0.27, p < 0.001). A total of 88.24% of participants lost more than 5% of their body weight. CONCLUSION: The combination of low dose of liraglutide and metformin was associated with significant reduction of body weight in Chinese Han women with PCOS. Additionally, a larger randomized double-blind multicenter controlled clinical trial is needed to confirm that. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn as ChiCTR1900024384.

A multimodal imaging-based classification for pediatric diffuse intrinsic pontine gliomas.

OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.

Multiview Incomplete Knowledge Graph Integration with application to cross-institutional EHR data harmonization.

OBJECTIVE: The growing availability of electronic health records (EHR) data opens opportunities for integrative analysis of multi-institutional EHR to produce generalizable knowledge. A key barrier to such integrative analyses is the lack of semantic interoperability across different institutions due to coding differences. We propose a Multiview Incomplete Knowledge Graph Integration (MIKGI) algorithm to integrate information from multiple sources with partially overlapping EHR concept codes to enable translations between healthcare systems. METHODS: The MIKGI algorithm combines knowledge graph information from (i) embeddings trained from the co-occurrence patterns of medical codes within each EHR system and (ii) semantic embeddings of the textual strings of all medical codes obtained from the Self-Aligning Pretrained BERT (SAPBERT) algorithm. Due to the heterogeneity in the coding across healthcare systems, each EHR source provides partial coverage of the available codes. MIKGI synthesizes the incomplete knowledge graphs derived from these multi-source embeddings by minimizing a spherical loss function that combines the pairwise directional similarities of embeddings computed from all available sources. MIKGI outputs harmonized semantic embedding vectors for all EHR codes, which improves the quality of the embeddings and enables direct assessment of both similarity and relatedness between any pair of codes from multiple healthcare systems. RESULTS: With EHR co-occurrence data from Veteran Affairs (VA) healthcare and Mass General Brigham (MGB), MIKGI algorithm produces high quality embeddings for a variety of downstream tasks including detecting known similar or related entity pairs and mapping VA local codes to the relevant EHR codes used at MGB. Based on the cosine similarity of the MIKGI trained embeddings, the AUC was 0.918 for detecting similar entity pairs and 0.809 for detecting related pairs. For cross-institutional medical code mapping, the top 1 and top 5 accuracy were 91.0% and 97.5% when mapping medication codes at VA to RxNorm medication codes at MGB; 59.1% and 75.8% when mapping VA local laboratory codes to LOINC hierarchy. When trained with 500 labels, the lab code mapping attained top 1 and 5 accuracy at 77.7% and 87.9%. MIKGI also attained best performance in selecting VA local lab codes for desired laboratory tests and COVID-19 related features for COVID EHR studies. Compared to existing methods, MIKGI attained the most robust performance with accuracy the highest or near the highest across all tasks. CONCLUSIONS: The proposed MIKGI algorithm can effectively integrate incomplete summary data from biomedical text and EHR data to generate harmonized embeddings for EHR codes for knowledge graph modeling and cross-institutional translation of EHR codes.

Surgical management and clinical outcomes of cerebellar liponeurocytomas-a report of seven cases and a pooled analysis of individual patient data.

Cerebellar liponeurocytomas (CLPNs) are very rare, with very few studies on this disease. Their treatment protocol also remains unclear. To better understand the disease, we reviewed the clinical features and outcomes, and proposed a treatment protocol based on previously reported cases as well as cases from our institute. The clinical data were obtained from seven patients with pathologically confirmed CLPNs, who underwent surgical treatment at our institute between November 2011 and June 2021. We also reviewed the relevant literature and 75 patients with CLPNs were identified between September 1993 and June 2021. Risk factors for progression-free survival (PFS) were evaluated in the pooled cohort. Our cohort included four males and three females, with a mean age of 43.9 ± 14.5 years (range: 29-64 years). CLPNs were located in the lateral ventricle in three cases and in the cerebellum in four cases. All seven cases achieved gross total resection (GTR) and radiotherapy was administered to two cases. After a mean follow-up of 44.9 ± 44.4 months, all patients remained well, with no recurrence or death. Among the 75 patients reported in the literature, 35 were males and 40 were females, with a mean age of 46.2 ± 13.6 years (range: 6-77 years). Biopsy, GTR, and non-GTR were achieved in one (1.3%), 50 (66.7%), and 24 (32%) patients, respectively. Radiotherapy was administered to 16 cases and chemotherapy was administered to only one case. After a mean follow-up of 47.5 ± 51.5 months, three patients died and tumor recurrence occurred in 17 patients. Multivariate Cox analysis revealed that non-GTR predicted a poor PFS (p = 0.020), and postoperative radiotherapy could not prolong PFS (p = 0.708). Kaplan-Meier analysis also showed that GTR was significantly associated with longer PFS (p = 0.008), and postoperative radiotherapy could not prolong PFS (p = 0.707). PFS rates at 1, 5, 10 years were 92.7%, 78.0%, 23.8% respectively. CLPNs are very rare brain tumors. Although they have favorable clinical prognosis, the recurrence is relatively high. GTR should be the first choice for treatment and close follow-up is necessary. Postoperative radiotherapy could not improve PFS in this study. A larger cohort is needed to verify our findings.

[A method of lung puncture path planning based on multi-level constraint].

Percutaneous pulmonary puncture guided by computed tomography (CT) is one of the most effective tools for obtaining lung tissue and diagnosing lung cancer. Path planning is an important procedure to avoid puncture complications and reduce patient pain and puncture mortality. In this work, a path planning method for lung puncture is proposed based on multi-level constraints. A digital model of the chest is firstly established using patient's CT image. A Fibonacci lattice sampling is secondly conducted on an ideal sphere centered on the tumor lesion in order to obtain a set of candidate paths. Finally, by considering clinical puncture guidelines, an optimal path can be obtained by a proposed multi-level constraint strategy, which is combined with oriented bounding box tree (OBBTree) algorithm and Pareto optimization algorithm. Results of simulation experiments demonstrated the effectiveness of the proposed method, which has good performance for avoiding physical and physiological barriers. Hence, the method could be used as an aid for physicians to select the puncture path.

Inhibition of METTL3/m6A/miR126 promotes the migration and invasion of endometrial stromal cells in endometriosis†.

N 6-methyladenosine (m6A), one of the most abundant RNA modifications, is involved in the progression of many diseases, but its role and related molecular mechanisms in endometriosis remain unknown. To address these issues, we detected m6A levels in normal, eutopic, and ectopic endometrium and found the m6A levels decreased in eutopic and ectopic endometrium compared with normal endometrium. In addition, we proved that methyltransferase-like 3 (METTL3) downregulation accounted for m6A reduction in endometriosis. Furthermore, we observed that METTL3 knockdown facilitated the migration and invasion of human endometrial stromal cells (HESCs), whereas METTL3 overexpression exerted opposite effects, suggesting that METTL3 downregulation might contribute to endometriosis development by enhancing cellular migration and invasion. Mechanistically, METTL3-dependent m6A was involved in the DGCR8-mediated maturation of primary microRNA126 (miR126 and pri-miR126). Moreover, miR126 inhibitor significantly enhanced the migration and invasion of METTL3-overexpressing HESCs, whereas miR126 mimics attenuated the migration and invasion of METTL3-silenced HESCs. Our study revealed the METTL3/m6A/miR126 pathway, whose inhibition might contribute to endometriosis development by enhancing cellular migration and invasion. It also showed that METTL3 might be a novel diagnostic biomarker and therapeutic target for endometriosis.

[Design of functional array electrode stimulation system with surface electromyography feedback].

In order to solve the problems of insufficient stimulation channels and lack of stimulation effect feedback in the current electrical stimulation system, a functional array electrode electrical stimulation system with surface electromyography (sEMG) feedback was designed in this paper. Firstly, the effectiveness of the system was verified through in vitro and human experiments. Then it was confirmed that there were differences in the number of amperage needed to achieve the same stimulation stage among individuals, and the number of amperage required by men was generally less than that of women. Finally, it was verified that the current required for square wave stimulation was smaller than that for differential wave stimulation if the same stimulation stage was reached. This system combined the array electrode and sEMG feedback to improve the accuracy of electrical stimulation and performed the whole process recording of feedback sEMG signal in the process of electrical stimulation, and the electrical stimulation parameters could change with the change of the sEMG signal. The electrical stimulation system and sEMG feedback worked together to form a closed-loop electrical stimulation working system, so as to improve the efficiency of electrical stimulation rehabilitation treatment. In conclusion, the functional array electrode electrical stimulation system with sEMG feedback developed in this paper has the advantages of simple operation, small size and low power consumption, which lays a foundation for the introduction of electrical stimulation rehabilitation treatment equipment into the family, and also provides certain reference for the development of similar products in the future.

Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (DiffCoEx) analysis were performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis. Modules and hub genes for bronchiolitis and emphysema were identified, and we found that genes in modules linked to neutrophil degranulation, Rho protein signal transduction and B cell receptor signalling were coexpressed in emphysema. DiffCoEx analysis showed that four hub genes (IFT88, CCDC103, MMP10 and Bik) were consistently expressed in emphysema patients; these hub genes were enriched, respectively, for functions of cilium assembly and movement, proteolysis and apoptotic mitochondrial changes. In our re-analysis of GSE69818, gene expression networks in relation to emphysema deepen insights into the molecular mechanism of COPD and also identify some promising therapeutic targets.

Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model.

Acute lung injury (ALI) is a severe disease with sudden onset, rapid progression, poor treatment response, and high mortality. An increasing number of studies had found that circular RNAs (circRNAs) has significant functions in various diseases, while the role of circRNAs in ALI is not yet clear. The purpose of this study was to find circRNAs related to ALI and their mechanism of action. Expression profiles of lung circRNAs and messenger RNAs (mRNAs) were analyzed by microarray in the ALI mice models and healthy controlled mice. Differentially expressed RNAs were identified, function and pathways were analyzed by bioinformatics analysis. Moreover, the results of the microarray were verified by real-time PCR. We identified 2262 differentially expressed mRNAs and 581 circRNAs between ALI mice and control. Validation of candidate circRNAs by real-time PCR indicates that the majority of circRNAs identified by microarray are reliable and worthy of further study. ALI induced circRNAs primarily function in the metabolic regulatory process. Moreover, differentially expressed circRNAs were mainly involved in signaling pathways of mitogen-activated protein kinases, focal adhesion, FoxO, neurotrophin, and Wnt. In addition, a competitive endogenous RNA network was constructed to further interpret the molecular mechanism of ALI. This study observed significantly changed circRNAs profiles in LPS-induced mouse model and revealed a potential role of circRNAs in ALI.

How hsa-miR-495 performed in the tumorigenesis of pancreatic adenocarcinoma by bioinformatics analysis.

INTRODUCTION: Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world for early metastasis, extensive invasion, and poor prognosis with a 5-year survival rate less than 5%. However, the underlying mechanisms are poorly understood. Therefore, it is urgent to explore molecular markers for early diagnosis or therapy target to improve the outcome of PAAD. METHODS: We retrieved transcriptome data as well as clinical information from patients with PAAD in The Cancer Genome Altas (TCGA) database. Survival time associated microRNAs (miRNAs) and messenger RNAs (mRNAs) were initially identified, followed by enrichment analysis (Gene Ontology [GO] and pathway). The relationship between survival time associated miRNAs-mRNAs was also investigated to discover putative transcriptional control mechanisms of PAAD. Finally, by consulting the literature and retrieving the database, we found that hsa-miR-495 might have played an important role in PAAD. RESULTS: In total, 146 miRNAs from 378 miRNAs and 580 mRNA from 17 100 mRNA, including 328 risk mRNA and 252 protective mRNA, were found to be associated with the survival time of PAAD. Eight hundred eighty-eight mRNA-miRNA pairs were related to the survival time of PAAD, involving in 755 mRNAs and 35 miRNAs. We chose 13 miRNAs predicted by target gene in the miRanda database for further research. Among these 13 miRNAs, hsa-miR-495 was identified as a good biomarker. Through GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significantly enriched pathways involved in focal adhesion, Staphylococcus aureus infection, and Intestinal immune network for immunoglobulin A production. And four target genes and 87 pathways of the hsa-miR-495 were enriched in PAAD. Interestingly, we found hsa-miR-495 with a low expression having a poor overall survival and significantly different recurrence rate within 5 years. CONCLUSION: Hsa-miR-495 and its target genes may serve as a prognostic and predictive marker in PAAD. Further research on the function of the hsa-miR-495 and its target genes in the KEGG pathway may provide references for treatment of PAAD.

Multidetector computed tomography angiography prior to bronchial artery embolization helps detect culprit ectopic bronchial arteries and non-bronchial systemic arteries originating from subclavian and internal mammary arteries and improve hemoptysis-free early survival rate in patients with hemoptysis.

OBJECTIVES: To compare the average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate between hemoptysis patients with multidetector computed tomography (MDCT) angiography prior to bronchial artery embolization (BAE) and those without preprocedural MDCT angiography METHODS: This retrospective study was approved by the institutional review board with waiver of patient informed consent. From September 2012 to March 2017, 157 consecutive hemoptysis patients had been undergoing BAE. Among them, 106 patients received preprocedural MDCT angiography (MDCT group), while 51 patients did not receive preprocedural MDCT angiography (control group). The average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate were compared between the two groups. RESULTS: The average number of culprit ectopic bronchial arteries and that of non-bronchial systemic arteries originating from the subclavian and internal mammary arteries per patient in the MDCT group were both significantly higher than those in the control group (0.15 ± 0.51 vs 0.04 ± 0.20, p = 0.022, and 0.17 ± 0.56 vs 0.08 ± 0.39, p = 0.040, respectively). The clinical success rate of BAE with preprocedural MDCT angiography tended to be higher than that without MDCT angiography (97.2 vs 88.2%, p = 0.057). Importantly, patients in the MDCT group had a significantly higher hemoptysis-free early survival rate compared to those in the control group (96.1 vs 86.7%, p = 0.031). CONCLUSIONS: Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and non-bronchial systemic arteries originating from subclavian and internal mammary arteries during BAE, and can improve the hemoptysis-free early survival rate, which could be recommended as a regular examination prior to BAE in patients with hemoptysis. KEY POINTS: • Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and NBSAs originating from subclavian and internal mammary arteries during BAE. • Conducting MDCT angiography prior to BAE can improve hemoptysis-free early survival rate in hemoptysis patients.