DeepIRES: a hybrid deep learning model for accurate identification of internal ribosome entry sites in cellular and viral mRNAs.

The internal ribosome entry site (IRES) is a cis-regulatory element that can initiate translation in a cap-independent manner. It is often related to cellular processes and many diseases. Thus, identifying the IRES is important for understanding its mechanism and finding potential therapeutic strategies for relevant diseases since identifying IRES elements by experimental method is time-consuming and laborious. Many bioinformatics tools have been developed to predict IRES, but all these tools are based on structure similarity or machine learning algorithms. Here, we introduced a deep learning model named DeepIRES for precisely identifying IRES elements in messenger RNA (mRNA) sequences. DeepIRES is a hybrid model incorporating dilated 1D convolutional neural network blocks, bidirectional gated recurrent units, and self-attention module. Tenfold cross-validation results suggest that DeepIRES can capture deeper relationships between sequence features and prediction results than other baseline models. Further comparison on independent test sets illustrates that DeepIRES has superior and robust prediction capability than other existing methods. Moreover, DeepIRES achieves high accuracy in predicting experimental validated IRESs that are collected in recent studies. With the application of a deep learning interpretable analysis, we discover some potential consensus motifs that are related to IRES activities. In summary, DeepIRES is a reliable tool for IRES prediction and gives insights into the mechanism of IRES elements.

Genome-wide perturbations of A-to-I RNA editing dysregulated circular RNAs promoting the development of cervical cancer.

Cervical cancer, the second most common female malignant tumor, seriously threatens women's health and lives. Despite the availability of the HPV vaccine, effective treatment options for cervical cancer are still lacking. New research perspectives now clarify that RNA editing dysregulation and changes in circRNA expression are jointly involved in disease pathogenesis, so molecular changes associated with circRNA and RNA editing may provide clues for the development of new therapeutic strategies for cervical cancer. In this study, we designed a series of pipelines to identify and analyze dysregulated RNA editing events in circRNAs. Our findings indicate a decrease in A-to-I RNA editing levels in cervical cancer compared to normal tissues, and editing may influence the back-splicing process of circRNAs through structural modifications of Alu elements. Moreover, our research reveals that RNA editing could modulate circRNA biogenesis by influencing RNA binding protein (RBP) binding on a transcriptome-wide scale, as well as influence the expression and coding potential of circRNAs. Importantly, we identified three RNA editing sites that could serve as potential biomarkers. In summary, our study presents a comprehensive landscape of RNA editing perturbations in circRNAs, providing new insights into the complex relationship between RNA editing and circRNA dysregulation in cervical cancer.

Alteration of the N6-methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome.

OBJECTIVE: To explore the N6-methyladenosine (m6A) methylation abnormality of mRNAs and its potential roles in the mouse model of polycystic ovary syndrome (PCOS). METHODS: The mouse model of PCOS were induced by injecting dehydroepiandrosterone (DHEA), and confirmed by observing the morphological structures of ovarian follicles. Subsequently, m6A-tagged mRNAs were identified via m6A epitranscriptomic microarray and its potential functional pathways were predicted in KEGG database. The expression and modification levels of key mRNAs in the most enriched pathway were evaluated and compared using western blot and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR). RESULTS: Compared with the control group, 415 hypermethylated and downregulated mRNAs, 8 hypomethylated and upregulated mRNAs, and 14 hypermethylated and upregulated mRNAs were identified in the PCOS group (Fold change ≥ 1.5). Those mRNAs were mainly involved in insulin signaling pathway, type II diabetes mellitus, Fc epsilon RI signaling pathway, inositol phosphate metabolism, and GnRH secretion. In insulin signaling pathway, the expression levels of phosphorylated protein kinase B (p-AKT) were decreased, whereas that of upstream phosphorylated phosphatidylinositol 3-kinase (p-PI3K) were increased in PCOS group. Moreover, skeletal muscle and kidney-enriched inositol polyphosphate 5-phosphatease (SKIP), one of PIP3 phosphatases, was verified to be overexpressed, and Skip mRNAs were hypermethylated in PCOS group. CONCLUSION: The altered m6A modification of mRNAs might play a critical role in PCOS process. The PI3K/AKT pathway is inhibited in the mouse model of PCOS. Whether it is caused by the m6A modification of Skip mRNAs is worthy of further exploration.

In-depth characterization and identification of translatable lncRNAs.

Long non-coding RNAs (LncRNAs) are non-protein coding transcripts more than 200 nucleotides in length. Deep sequencing technologies have unveiled lncRNAs can harbor translatable short open reading frames (sORFs). Yet the regulatory mechanisms governing lncRNA translation events remain poorly understood. Here, we exhaustively detected the sequence, functional element, and structure features relevant to lncRNA translation in human. Extensive identification and analysis reveal that translatable lncRNAs contain richer protein-coding related sequence features, cap-dependent and cap-independent translation initiation mechanisms, and more stable secondary structures, as compared to untranslatable lncRNAs. These findings strongly support lncRNAs serve as a repository for the production of new small peptides. Based on the feature fusion affecting translation and the extreme gradient boosting (XGBoost) algorithm, we developed the first computational tool that dedicated for predicting translatable lncRNAs, named TransLncPred. Benchmark experimental results show that our method outperforms several state-of-the-art RNA coding potential prediction tools on the same training and testing datasets. The 100-time 10-fold cross-validation tests also demonstrate that regulatory element-derived features, especially N7-methylguanosine (m7G) and internal ribosome entry site (IRES), contribute to the improvement in predictive performance.

Clinical features of the predilection and severer sites of intrauterine adhesions. / å®«è ”ç²˜è¿žå¥½å‘å’Œç›¸å¯¹ä¸¥é‡éƒ¨ä½çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Intrauterine adhesions (IUA) refers to the adhesions between the myometrium of the uterine cavity, which is secondary to damage to the basal layer of the endometrium due to trauma or infection. The occurrence of IUA is mainly related to intrauterine operations. Hysteroscopic adhesiolysis (HA) is the standard surgical treatment for IUA. But the recurrence rate of IUA after HA is still high. Importantly, endometrium recovery is difficult, resulting in unsatisfied prognosis for moderate to severer IUA patients. Therefore, it is important to take effective primary preventive measures against the etiology to avoid endometrium damage from medical surgery. In this paper, we discuss and analyze predilection and severer sites of intrauterine adhesions, aiming to provide a basis for how to avoid and reduce injuries during intrauterine operations, such as abortion, dilation and curettage. METHODS: In this study, we retrospectively analyzed the surgical videos of patients who underwent HA for the first time from January 2019 to December 2021 in the Third Xiangya Hospital of Central South University so as to assess the area of adhesions and predilection and severer sites of occurrence of adhesions, and we collected 657 patients who underwent HA for the first time, including 81 patients with total IUA and 576 patients with partial IUA. We counted and analyzed the number and composition ratio of partial IUA patients with severer sites of damage to the lateral wall of the uterine cavity and severerr sites of damage to each segment of the uterine cavity. RESULTS: Among 576 patients with partial IUA, there were 60 patients with no significant difference in the degree of adhesions between the right and left sides, 143 patients with severer adhesions on the left side of the uterine cavity, and 373 patients with severer adhesions on the right side of the uterine cavity. There was a difference in the severity of damage of left and right lateral wall. The proportion of patients with severer adhesions on the right side of the uterine cavity (64.8%) was higher than that of patients with adhesions on the left side of the uterine cavity (24.8%), and there was statistically difference (P<0.05). There was 93 patients with severer adhesions at the fundus or bilateral horn of the uterus, 190 patients with severer adhesions at the middle and upper part of the uterine cavity, 245 patients with severer adhesions at the middle and lower part of the uterine cavity and at the endocervix, and 48 patients with no significant difference in the degree of adhesions in each part. The proportion of patients with severer adhesions at the middle and lower part of the uterine cavity and at the endocervix was higher (42.5%) than those with adhesions in the fundus or bilateral horn of the uterus (16.1%) and in the middle and upper part of the uterine cavity (33.0%), and there were statistically differences (both P<0.05). CONCLUSIONS: The predilection site of IUA is the lateral wall of the uterine cavity. The severer adhesions is in the right lateral wall of the uterine cavity, the middle and lower segments and the endocervix, which may be related to the operating habits of the surgeon. Therefore, gynecologists should minimize damage to the lateral wall of the uterine cavity, especially the right lateral wall in performing uterine operations (more attention should be paid by right-handed physicians). Besides, we should pay attention to protecting the middle and lower segments of the uterine cavity and the endocervix, avoiding maintaining negative pressure to withdraw the uterine tissue suction tube from the uterine cavity during abortion procedures to minimize damage.

Preliminary study on the advantages of hysteroscopic myomectomy with cold knife. / å®«è ”é•œä¸‹å†·åˆ€åˆ‡é™¤é»è†œä¸‹è‚Œç˜¤ä¼˜åŠ¿çš„åˆæ­¥æŽ¢è®¨.

OBJECTIVES: At present, hysteroscopic submucosal fibroids resection is mostly performed by hysteroscopic electric resection (hereinafter referred to as electric knife). During the operation, the electrothermal effect could not only damage the endometrial tissues covered by the surface of the fibroid, but also easily damage the endometrial tissues around the fibroid, which is very unfavorable for patients with fertility requirements. In addition, for some special fibroids (located at horn and fundus) or Type II and multiple submucosal fibroids, the traditional electric resection is still very difficult. With the opening of the second-child policy and the urgent desire of patients for fertility, more and more attention is paid to the concept of fertility protection in China. Therefore, hysteroscopic cold knife technology (hereinafter referred to as cold knife) has gradually entered the vision. The cold knife has the advantages of simple operation, such as little trauma and quick postoperative recovery. In this study, the advantages of cold knife in the surgical resection of submucosal fibroids are discussed by comparing the safety and effectiveness between the hysteroscopic cold knife resection (hereinafter referred to as cold knife) and the electric knife resection in the submucosal fibroids. METHODS: The clinical data of 112 patients with submucosal fibroids diagnosed and treated by hysteroscopic surgery at the Third Xiangya Hospital of Central South University from January 2017 to October 2021 were retrospectively analyzed, including preoperative general information (such as age, gravidity, abortion times, the size, location, type and number of submucosal fibroids, preoperative hemoglobin value) and intraoperative conditions [such as intraoperative bleeding, the operation time, residual rates and intraoperative complications (massive bleeding, perforation, water poisoning)]. The patients were divided into a cold knife group and an electric knife group, and there were 40 cases in the cold knife group and 72 cases in the electric knife group. The postoperative complications and the pregnancy outcomes in the 2 groups were followed up by telephone, the follow-up data included postoperative recurrence rate, pregnancy rate, pregnancy mode, and pregnancy outcome. RESULTS: Compared with the electric knife group, the cold knife group had more submucous myomas located in the horn or fundus of the uterus (9.7% vs 25.0%), and more Type II myomas or combined with Type II myomas (26.4% vs 70.0%). However, there were no significant difference in intraoperative bleeding, the operation time, intraoperative complications and the residual rates between the 2 groups (all P>0.05). A total of 98 patients were followed up, including 32 patients in the cold knife group and 66 patients in the electric knife group. Compared with the electric knife group, there were lower postoperative complications in the cold knife group (12.5% vs 37.9%) (P<0.05). Among the 7 patients with multiple submucosal fibroids (the number of fibroids ≥5), there were 4 patients in the electric knife group and 3 patients in the cold knife group. In the electric knife group, the postoperative menstrual volume in the 4 patients was significantly reduced and 3 patients had postoperative fertility requirements, which were all diagnosed as intrauterine adhesion by hysteroscopy and performed further surgery. Later, 2 patients had successful pregnancy, 1 had miscarriage, and 1 had full-term spontaneous labor. However, the menstrual volume of the 3 patients in the cold knife group was not significantly reduced compared with normal menstrual volume, and 2 of them had fertility requirements, and they had natural pregnancy and full term vaginal delivery. There were no significant differences in postoperative recurrence rate, pregnancy rate, pregnancy mode and pregnancy outcome between the 2 groups (all P>0.05). CONCLUSIONS: Both the electric knife and cold knife resection are safe and effective methods for the treatment of submucosal fibroids. Compared with electric knife resection, the cold knife resection has fewer postoperative complications and perhaps more advantages in endometrial protection, especially for the patients with fertility requirements, submucosal fibroids located at the fundus or horn of the uterus, Type II submucosal fibroids, and multiple submucosal fibroids.

Hysteroscopic dilation techniques in hysteroscopic adhesiolysis. / é•œä¸‹æ‰©å®«æ³•åœ¨å®«è ”é•œå®«è ”ç²˜è¿žåˆ†ç¦»æœ¯ä¸­çš„åº”ç”¨.

OBJECTIVES: Intrauterine adhesion (IUA) is mainly caused by intrauterine operations such as pregnancy-related curettage and hysteroscopic surgery, resulting in the trauma to the basal layer of the endometrium. Hysteroscopic adhesiolysis is a crucial step in the comprehensive treatment of IUA, and the most common complication is uterine perforation. More than half of all uterine perforations occur during the hysteroscopy or probe/dilator pass through the internal os. Furthermore, inappropriate surgical procedures may lead to endometrial injury, recurrence or even aggravation of adhesions, and complications such as cervix laceration and false passage formation. This study aims to explore the usage of the hysteroscopic dilatation techniques to dilate the internal os and lower uterine segment, which is via hysteroscopy entering the internal os laterally and swinging, or by directly opening the forceps or scissors and bluntly spreading dissection under direct hysteroscopic vision. By using the hysteroscopic dilatation techniques, we intend to improve the effectiveness and safety of cervical dilation in patients with IUA in the internal os and/or lower uterine segment. METHODS: A total of 282 patients with adhesions in the internal os or lower uterine segment underwent HA in the Third Xiangya Hospital of Central South University from January 2020 to June 2021 were included, ranging from 21 to 46 (33.0±4.8) years old in age and 5 to 12 in the American Fertility Society score. Among them, there were 2 cases of false passage formation caused by traditional dilatation in other hospitals. All patients underwent hysteroscopy with integrated hysteroscopy with 5Fr instrument channel and 4.9 mm outer sheath diameter. The internal orifice of cervix and the lower segment of uterine cavity were dilated under the microscope. After the hysteroscopy entered the uterine cavity, the separation of uterine cavity adhesion and the placement of uterine contraceptive ring or uterine stent into the uterine cavity were performed routinely. Age, surgical records, and surgical videos of all included cases were collected. The success rate of dilation and the incidence of surgical complications were assessed. RESULTS: In all cases, the hysteroscopys successfully entered into the uterine cavity by using the hysteroscopic dilatation techniques without failure and switching to cervical dilators. In the 2 cases of false passage due to previous cervical dilation, the uterine cavity was identified and found successfully under direct hysteroscopic vision. During the whole surgery, the vision was clear, and no complications (such as cervix laceration, false passage formation, uterine perforation or water intoxication) occurred. One to 3 months postoperative hysteroscopy revealed no significant fibrotic stenosis in the internal os and lower uterine segment. CONCLUSIONS: The hysteroscopic dilation techniques are a strategy for separation methods that is following structural hierarchy anatomy in the mode of "see and treat" for the adhesion in the internal os and uterine cavity under direct hysteroscopic vision. This method not only has ultrasound guidance, but also has the judgment of structural hierarchy anatomy under direct hysteroscopic vision, so there is less chance of anatomical level judgment error. This method makes full use of the hysteroscopic judgement of the experienced hysteroscopic surgeons, so that surgeons can timely find and avoid re-entering the old false passage caused by previous surgery. The adhesions in the internal os and lower uterine segment were separated by the hysteroscopic dilation techniques. In this way, the damage to the endometrium caused by forced insertion of the hysteroscopy can be avoided. Meticulous separation of adhesions and cervical dilation under direct hysteroscopic vision can effectively reduce the occurrence of surgical complications such as false passage formation, cervical laceration, and uterine perforation. The use of mini-hysteroscopy eliminates the need for preoperative cervical preparation, avoiding associated risks and side effects. Moreover, for patients with adhesions in the internal os and lower uterine segment, preoperative cervical preparation is not effective in cervical dilation, while the hysteroscopic dilation techniques are effective, with higher patient acceptance due to the absence of preoperative cervical preparation. For the skilled hysteroscopic surgeons, the hysteroscopic dilation technique is easy to operate and worthy of clinical application.

Comparison of high-intensity focused ultrasound ablation and uterine artery embolization in the management of cervical pregnancy.

Background: Cervical pregnancy (CP) is an uncommon type of ectopic pregnancy with a rising risk to life. Currently, there is no universal protocol for the safe and effective management of CP. This study aimed to investigate the clinical efficacy of high-intensity focused ultrasound ablation (HIFU) vs. uterine artery embolization (UAE) in the management of CP to develop a standard for the treatment of CP. Methods: From January 2015 to October 2021, 36 patients with CP were diagnosed, treated, and followed up at the Department of Gynecology of Third Xiangya Hospital of Central South University. A total of 11 patients were treated with HIFU followed by suction curettage under hysteroscopic guidance, and 25 patients were treated with UAE followed by suction curettage under hysteroscopic guidance. Medical records and pregnancy outcomes were retrospectively analyzed. Results: Compared to the UAE group, the HIFU group had a shorter interval time (1.5 ± 0.21 days vs. 2.6 ± 0.26 days), shorter duration of hospitalization (5.5 ± 0.31 days vs. 6.6 ± 0.21 days), shorter recovery time of menstruation (30.6 ± 7.09 days vs. 36.9 ± 5.54 days), fewer adverse reactions (0/11 vs. 9/25), and fewer postoperative complications (1/11 vs. 8/25). There were no significant differences in age, gravidity, parity, abortion, gestational age, cardiac pulsation, admission symptoms, hemoglobin level, largest diameter of the sac/mass, serum human chorionic gonadotropin (hCG) level at admission, hospitalization expenses, hospitalization days, blood loss during curettage, degree of hCG decline, residue after curettage, fertility requirement, and pregnancy outcomes. Conclusion: Both HIFU and UAE are safe and effective in the treatment of patients with CP. Compared to UAE, HIFU treatment for CP is a safer and more effective therapeutic schedule owing to the advantages of being more minimally invasive, shorter interval time, shorter hospitalization days and recovery time of menstruation, fewer adverse reactions, and fewer postoperative complications.

Identification of Alternative Splicing-Related Genes CYB561 and FOLH1 in the Tumor-Immune Microenvironment for Endometrial Cancer Based on TCGA Data Analysis.

Background: Advanced and recurrent endometrial cancer EC remains controversial. Immunotherapy will play a landmark role in cancer treatment, and alternative splicing (AS) of messenger RNA (mRNA) may offer the potential of a broadened target space. Methods: We downloaded the clinical information and mRNA expression profiles from The Cancer Genome Atlas (TCGA) database. Hub genes were extracted from 11 AS-related genes to analyze the correlation between clinical parameters and the tumor-immune microenvironment. We also analyzed the correlations between the copy numbers, gene expressions of hub genes, and immune cells. The correlation between the risk score and the six most important checkpoint genes was also investigated. The ESTIMATE algorithm was finally performed on each EC sample based on the high- and low-risk groups. Results: The risk score was a reliable and stable independent risk predictor in the Uterine Corpus Endometrial Carcinoma (UCEC) cohort. CYB561|42921|AP and FOLH1|15817|ES were extracted. The expression of CYB561 and FOLH1 decreased gradually with the increased grade and International Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.05). Gene copy number changes in CYB561 and FOLH1 led to the deletion number of myeloid DC cells and T cell CD8+. Low expression of both CYB561 and FOLH1 was associated with poor prognosis (p < 0.001). The checkpoint genes, CTLA-4 and PDCD1, exhibited a negative correlation with the risk score of AS in UCEC. Conclusion: AS-related gene signatures were related to the immune-tumor microenvironment and prognosis. These outcomes were significant for studying EC's immune-related mechanisms and exploring novel prognostic predictors and precise therapy methods.

A Novel Nomogram Based on 3-dimensional Transvaginal Ultrasound for Differential Diagnosis Between Severe and Mild-to-Moderate Intrauterine Adhesions.

STUDY OBJECTIVE: To develop and validate a nomogram for differentiating severe intrauterine adhesions (IUAs) from mild-to-moderate IUAs preoperatively on the basis of 3-dimensional transvaginal ultrasound (3D-TVUS). DESIGN: Retrospective observational study. SETTING: University-affiliated hospital. PATIENTS: A dataset of 413 patients who had undergone hysteroscopic adhesiolysis and 3D-TVUS examination before hysteroscopic adhesiolysis between March 2019 and December 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 212 patients with mild-to-moderate IUAs and 201 patients with severe IUAs were enrolled. Intercornual distance, endometrial thickness, number of visible fallopian tubal ostia, echoes of the endometrial-myometrial junction zone, and endometrial blood flow grade differed significantly between the severe and mild-to-moderate IUAs groups. The area under the receiver operating characteristic curve of the nomogram was 0.880 (95% confidence interval, 0.843-0.918) in the training set and 0.878 (95% confidence interval, 0.818-0.939) in the validation set, revealing reliable discrimination. The calibration curve and Hosmer-Lemeshow test showed strong calibration, and decision curve analysis indicated that the nomogram had a high net benefit and a wide range of threshold probabilities. CONCLUSION: This nomogram, which was developed on the basis of 3D-TVUS, can accurately distinguish severe IUAs from mild-to-moderate IUAs preoperatively.

Machine Learning Algorithms Identify Clinical Subtypes and Cancer in Anti-TIF1γ+ Myositis: A Longitudinal Study of 87 Patients.

BACKGROUND: Anti-TIF1γ antibodies are a class of myositis-specific antibodies (MSAs) and are closely associated with adult cancer-associated myositis (CAM). The heterogeneity in anti-TIF1γ+ myositis is poorly explored, and whether anti-TIF1γ+ patients will develop cancer or not is unknown at their first diagnosis. Here, we aimed to explore the subtypes of anti-TIF1γ+ myositis and construct machine learning classifiers to predict cancer in anti-TIF1γ+ patients based on clinical features. METHODS: A cohort of 87 anti-TIF1γ+ patients were enrolled and followed up in Xiangya Hospital from June 2017 to June 2021. Sankey diagrams indicating temporal relationships between anti-TIF1γ+ myositis and cancer were plotted. Elastic net and random forest were used to select and rank the most important variables. Multidimensional scaling (MDS) plot and hierarchical cluster analysis were performed to identify subtypes of anti-TIF1γ+ myositis. The clinical characteristics were compared among subtypes of anti-TIF1γ+ patients. Machine learning classifiers were constructed to predict cancer in anti-TIF1γ+ myositis, the accuracy of which was evaluated by receiver operating characteristic (ROC) curves. RESULTS: Forty-seven (54.0%) anti-TIF1γ+ patients had cancer, 78.7% of which were diagnosed within 0.5 years of the myositis diagnosis. Fourteen variables contributing most to distinguishing cancer and non-cancer were selected and used for the calculation of the similarities (proximities) of samples and the construction of machine learning classifiers. The top 10 were disease duration, percentage of lymphocytes (L%), percentage of neutrophils (N%), neutrophil-to-lymphocyte ratio (NLR), sex, C-reactive protein (CRP), shawl sign, arthritis/arthralgia, V-neck sign, and anti-PM-Scl75 antibodies. Anti-TIF1γ+ myositis patients can be clearly separated into three clinical subtypes, which correspond to patients with low, intermediate, and high cancer risk, respectively. Machine learning classifiers [random forest, support vector machines (SVM), extreme gradient boosting (XGBoost), elastic net, and decision tree] had good predictions for cancer in anti-TIF1γ+ myositis patients. In particular, the prediction accuracy of random forest was >90%, and decision tree highlighted disease duration, NLR, and CRP as critical clinical parameters for recognizing cancer patients. CONCLUSION: Anti-TIF1γ+ myositis can be separated into three distinct subtypes with low, intermediate, and high risk of cancer. Machine learning classifiers constructed with clinical characteristics have favorable performance in predicting cancer in anti-TIF1γ+ myositis, which can help physicians in choosing appropriate cancer screening programs.

Characteristics and transcriptomic analysis of scar tissues on the inner uterine cavity wall in patients with intrauterine adhesions.

Introduction: It has been previously reported that intrauterine adhesions (IUAs) are the main cause of uterine infertility. However, the histological origin of scar tissue present on the inner wall of the uterine cavity with IUAs has not been previously studied, which is particularly necessary for follow-up research and prevention and treatment. Methods: In this study, myometrium with normal uterus were assigned to the control group and scar tissues with IUAs were assigned to the experimental group. And pathological characteristics and transcriptomic were analyzed between the two groups. Results: We founded no difference was noted in the histological morphology and the α-SMA expression between the experimental and control groups. A total of 698 differentially expressed genes were identified between the two groups. Gene Ontology (GO) analyses revealed that the DEGs were significantly enriched in cell proliferation, AP-1 complex formation, and angiogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the target genes were significantly enriched in the AGE-RAGE, FOXO and TNF signaling pathway. Discussion: As far as we know, this is the first study to propose that the scar tissues are mainly derived from the myometrium and the first one to report differentially expressed genes in the scar tissues of IUAs.

Comparison of ultrasound-guided high-intensity focused ultrasound ablation and hysteroscopic myomectomy for submucosal fibroids: a retrospective study.

OBJECTIVE: To compare the safety, reintervention and pregnancy outcomes between ultrasound-guided high intensity focused ultrasound (USgHIFU) and hysteroscopic myomectomy (HM) for submucosal fibroids. MATERIALS AND METHODS: A total of 215 patients with a solitary submucosal fibroid treated by USgHIFU or HM at the third Xiangya Hospital were retrospectively reviewed. Among them, 58 treated with USgHIFU, 157 treated with HM. RESULTS: A significant difference was observed in size, location and type of the fibroids, effective rate, and cumulative reintervention rate between the two groups (p < .05). The size of the fibroids was 57.9 ± 1.9 mm in the USgHIFU group, while it was 32.6 ± 1.2 mm in the HM group. The number of the fibroids at horn or fundus/uterine cavity was 16/42 in the USgHIFU group, while it was 21/136 in the HM group. The number of type I/II/2-5 was 16/17/25 in the USgHIFU group, while it was 133/24/0 in the HM group. In the USgHIFU group, the effective rate was 100% and the cumulative reintervention rate at 50 (17-97) months was 19.0%, while in the HM group, it was 94.3% and 7.6%, respectively. During the follow-up period, the pregnancy rate was 22.4% (13/58) and the reintervention rate due to invalid and recurrence was 15.5% (9/58) in the USgHIFU group, while they were 18.5% (29/157) and 7.0% (11/157) in the HM group. No significant difference was observed between the two groups (p > .05). Furthermore, the reintervention rate was positively correlated with age, treatment methods and parity and fertility requirements. No other significant difference was observed between the two groups. CONCLUSIONS: Both USgHIFU and HM are safe and effective in treating submucosal fibroids. Compared with the HM group, the USgHIFU group had lower postoperative complications, but higher reintervention rate, with similar recurrence rate, pregnancy rate and reintervention rate due to invalid and recurrence. Reintervention was related to age, treatment methods, parity and fertility requirements.

Comparative effectiveness of laparoscopic versus hysteroscopic approach in patients with previous cesarean scar defect: a retrospective cohort study.

BACKGROUND: The aim of this study was to evaluate the clinical effectiveness and obstetric outcomes of laparoscopic and hysteroscopic surgery in patients with previous cesarean scar defect (PCSD). METHODS: A retrospective cohort analysis was performed on women who underwent laparoscopic or hysteroscopic surgery for PCSD from 2016 to 2019 at the Third Xiangya Hospital of Central South University. Among these participants, 13 underwent laparoscopic surgery and 33 received hysteroscopic surgery. RESULTS: Significant differences were displayed in the operative times (156.9±42.3 vs. 40.7±38.9 min, P<0.05), intra-operative blood loss (80.0±61.0 vs. 17.9±51.2 mL, P<0.05), hospital stay (7.1±1.6 vs. 4.1±2.1 days, P<0.05), postoperative hospital stay (4.3±0.8 vs. 1.5±1.1 days, P<0.05), and hospitalization expenses (22,240.3±249.9 vs. 9,547.1±4,747.2 yuan, P<0.05) between the laparoscopic surgery and hysteroscopic group. No significant difference was observed in the incidence of clinical efficacy between the laparoscopic and hysteroscopic surgery group. A total of 2 of the 4 patients in the laparoscopic surgery group, and 9 of 11 patients in the hysteroscopic surgery group delivered successfully. All 2 participants in the laparoscopic surgery group and 2 participants in the hysteroscopic surgery group were diagnosed with placenta previa. No uterine rupture was reported in our study. CONCLUSIONS: Both laparoscopic and hysteroscopic surgery are safe and effective treatments for PCSD patients, and hysteroscopic surgery is more efficient for PCSD patients.

APMAP Promotes Epithelial-Mesenchymal Transition and Metastasis of Cervical Cancer Cells by Activating the Wnt/ß-catenin Pathway.

Cervical cancer is a malignant tumor of the female reproductive system. At present, its occurrence, development and transfer mechanism are not entirely clear. APMAP (Adipocyte Plasma Membrane Associated Protein) is a glycosyl type II transmembrane protein that is mainly distributed in the plasma membrane and endoplasmic reticulum of adipocytes. APMAP has been reported to be involved in lipid transport and can induce epithelial-mesenchymal transition of prostate cancer and the liver metastasis of colorectal cancer. However, the role of APMAP in cervical cancer is still unknown. We analyzed the expression and prognosis of APMAP using data in both the GEO and the TCGA databases. We analyzed the function of APMAP using Transwell, wound healing assay and flow cytometry, and assessed the main mechanisms of APMAP by RT-PCR and Western blotting. We found that APMAP was highly expressed in cervical cancer tissues, and patients with high expression had poor prognosis. The functional in vitro experiments demonstrated that APMAP knockdown significantly inhibited the migration ability of cervical cancer cells, but had little effect on cell apoptosis. Mechanically, APMAP promotes cervical cancer cell migration and epithelial-mesenchymal transition by activating the Wnt/ß-catenin pathway. Overall, APMAP is a potential prognostic marker as well as a therapeutic target of cervical cancer.

The characteristics and risk factors of human papillomavirus infection: an outpatient population-based study in Changsha, Hunan.

This cross-sectional study investigated the characteristics of cervical HPV infection in Changsha area and explored the influence of Candida vaginitis on this infection. From 11 August 2017 to 11 September 2018, 12,628 outpatient participants ranged from 19 to 84 years old were enrolled and analyzed. HPV DNA was amplified and tested by HPV GenoArray Test Kit. The vaginal ecology was detected by microscopic and biochemistry examinations. The diagnosis of Candida vaginitis was based on microscopic examination (spores, and/or hypha) and biochemical testing (galactosidase) for vaginal discharge by experts. Statistical analyses were performed using SAS 9.4. Continuous and categorical variables were analyzed by t-tests and by Chi-square tests, respectively. HPV infection risk factors were analyzed using multivariate logistic regression. Of the total number of participants, 1753 were infected with HPV (13.88%). Females aged ≥ 40 to < 50 years constituted the largest population of HPV-infected females (31.26%). The top 5 HPV subtypes affecting this population of 1753 infected females were the following: HPV-52 (28.01%), HPV-58 (14.83%), CP8304 (11.47%), HPV-53 (10.84%), and HPV-39 (9.64%). Age (OR 1.01; 95% CI 1-1.01; P < 0.05) and alcohol consumption (OR 1.30; 95% CI 1.09-1.56; P < 0.01) were found to be risk factors for HPV infection. However, the presence of Candida in the vaginal flora was found to be a protective factor against HPV infection (OR 0.62; 95% CI 0.48-0.8; P < 0.001). Comparing with our previous study of 2016, we conclude that the subtype distribution of HPV infection is relatively constant in Changsha. Our data suggest a negative correlation between vaginal Candida and HPV, however, more radical HPV management is required in this area for perimenopausal women and those who regularly consume alcohol.

HisPhosSite: A comprehensive database of histidine phosphorylated proteins and sites.

Histidine phosphorylation is critically important in a variety of cellular processes including signal transduction, cell cycle, proliferation, differentiation, and apoptosis. It is estimated to account for 6% of all phosphorylated amino acids. However, due to the acid lability of the PN bond, the study of pHis lags far behind that of pSer, pThr, and pTyr. Recently, the development and use of pHis-specific antibodies and methodologies have led to a resurgence in the study of histidine phosphorylation. Although a considerable number of pHis proteins and sites have been discovered, most of them have not been manually curated and integrated to any databases. There is a lack of a data repository for pHis, and such work is expected to help further systemic studies of pHis. Thus, we present a comprehensive resource database of histidine phosphorylation (HisPhosSite) by curating experimentally validated pHis proteins and sites and compiling putative pHis sites with ortholog search. HisPhosSite contains 776 verified pHis sites and 2702 verified pHis proteins in 38 eukaryotic and prokaryotic species and 15,378 putative pHis sites and 10,816 putative pHis proteins in 1366 species. HisPhosSite provides rich annotations of pHis sites and proteins and multiple search engines (including motif search and BLAST search) for users to locate pHis sites of interest. HisPhosSite is available at http://reprod.njmu.edu.cn/hisphossite. SIGNIFICANCE: Histidine phosphorylation is involved in a variety of cellular processes as well as cancers, and it has been proved to be more common than previously thought. The HisPhosSite database was developed to collect pHis data from published literatures with experimental evidences. Unification of the identified pHis proteins and sites will give researchers an informative resource for histidine phosphorylation. HisPhosSite has a user-friendly interface with multiple search engines for users to locate pHis sites of interest. In addition, the database provides rich structural and functional annotations. HisPhosSite will help future studies and elucidation of the functions of histidine phosphorylation.

Obstetrical outcome in the third trimester after hysteroscopic adhesiolysis.

BACKGROUND: Intrauterine adhesion (IUA) is caused by adhesion of the uterine cavity due to the damage of endometrium. Hysteroscopic adhesiolysis (HA) is the main treatment. The objective of the study was to investigate the obstetrical outcome in the third trimester of women who previously underwent HA. METHODS: We performed a retrospective cohort study in the university-affiliated hospital. A total of 146 women with a history of HA who had given birth in their third trimester from May 2012 to May 2019 were enrolled (study group), while 292 women with a negative history of HA were matched for maternal age, gravidity, parity, and delivery year. The parameters of obstetrics and infants were investigated to evaluate the change in the third trimester of women with a history of HA. RESULTS: There was no significant difference between study and control groups in gestational weeks, nor in fetal gender distribution, birth weight, Apgar score, fetal distress, and neonatal intensive care unit (NICU) admissions after delivery (P>0.05). In addition, when compared with the control group, women with a history of HA were at a higher risk of placental risks (P<0.05), such as placenta previa (11.6% versus 3.1%), abnormally invasive placenta (AIP) (33.56% versus 2.7%), and retained placenta (42.5% versus 8.6%). This resulted in a significantly higher postpartum hemorrhage (PPH) rate in the study group as compared with that in the control group (8.9% versus 1.0%, P<0.05). Such cases were more likely to be found in patients with severe IUA compared with those who were assessed as mild and moderate. CONCLUSIONS: The history of HA might be an important risk factor inducing placental problems and PPH in the third trimester. More attention should be paid to the labor of pregnant women with a history of HA.