Diagnosis of septate uterus. / 纵隔子宫的诊断（英文）.

The septate uterus is the most common structural uterine anomalies and it is associated with the poor reproductive outcome. It is believed to be the result of the failure in resorption of the tissue connecting the 2 paramesonephric ducts prior to the 20th embryonic week. The true prevalence of uterine septum is difficult to ascertain, as many uterine septal defects are asymptomatic. The septate uterus is usually diagnosed during an infertility evaluation and affects reproductive health by impairing fertility and increasing adverse pregnancy outcomes. The variations in uterine and cervical/vaginal anomalies collectively referred to as Müllerian anomalies. No consistent gold standard for the diagnosis of Müllerian anomalies exists. The preferred diagnostic method for Müllerian anomalies is two-dimensional ultrasound, other methods such as three-dimensional ultrasound, magnetic resonance imaging, hysterosalpingo contrast sonography, hysterosalpingography, hysteroscopy, and laparoscopy are also used to improve accuracy.

Uterine Cavity Parameters Evaluated by Hysteroscopy can Predict the Live Birth Rate For Intrauterine Adhesion Patients.

We aim to establish an objective and accurate prediction model by evaluating the uterine cavity and correlate these key factors with the live birth rate after hysteroscopic adhesiolysis (HA). A total of 457 intrauterine adhesions (IUA) patients were retrospectively enrolled in this study. The participants underwent HA and second-look hysteroscopy at the Third Xiangya Hospital of Central South University. Pregnancy outcomes, including spontaneous live births and no live births (miscarriages and infertility), were followed. Clinical parameters, containing the number of visible uterine horns and tubal ostia, the length of the uterine cavity, among others, were measured and analyzed to determine the dominant variables in an attempt to establish the live birth rate, prediction models. Women in the no live birth group were older than that in the live birth group (P = 0.0002, OR = 0.895, 95% CI: 0.844-0.949) and were more likely to be 2 gravidity (P = 0.0136, OR = 2.558, 95% CI: 1.213-5.394). Uterine cavity length in pre-HA hysteroscopy was longer in the live birth group (P = 0.0018, OR = 1.735, 95% CI: 1.227-2.453), and adhesion scores in pre-HA hysteroscopy were more frequently above 6 (P = 0.0252, OR = 0.286, 95% CI: 0.096-0.856) in the no live birth group. During the second-look, hysteroscopy, visible bilateral fallopian tube ostia were more frequently observed in the live birth group (P = 0.0339, OR = 11.76, 95% CI: 1.207-114.611), and adhesion scores were 4-6 (P < 0.0001, OR = 0.032, 95% CI: 0.007-0.146) and above 6 (P < 0.0001, OR = 0.012, 95% CI: 0.002-0.073) in the no live birth group. The areas under the curves (AUCs) of the pre-HA and second-look hysteroscopy prediction models were 0.7552 and 0.8484, respectively. We established an objective and accurate method for evaluating the uterine cavity by hysteroscopy, and second-look hysteroscopy is more valuable than the fist hysteroscopy in predicting the live birth rate following HA. Visible bilateral fallopian tube ostia or adhesion scores were <4 in the second-look hysteroscopy might predict live birth after surgery.

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.

ACTL6A knockdown inhibits cell migration by suppressing the AKT signaling pathway and enhances the sensitivity of glioma cells to temozolomide.

Molecular-targeted therapy has had a significant impact on glioma. Notably, actin-like 6A (ACTL6A) has been indicated to be essential for embryonic development and tumor progression. However, the role of ACTL6A in glioma remains unclear. The present study aimed to investigate the effects of ACTL6A on glioma cell migration and sensitivity to temozolomide (TMZ). The expression levels of ACTL6A were analyzed in patients with glioma, and survival curves were created using data from The Cancer Genome Atlas. U251 and T98G cells were transfected with short hairpin (sh)RNA for use in loss-of-function experiments to investigate the biological function and molecular mechanisms of ACTL6A. Furthermore, an MTT assay was used to assess the effect of ACTL6A on the sensitivity of glioma cells to TMZ. The results demonstrated that ACTL6A was expressed at higher levels in glioma tissues compared with normal brain tissues. Furthermore, high expression of ACTL6A was associated with a poor prognosis. The knockdown of ACTL6A significantly inhibited the migration phenotype in glioma cells and significantly decreased the levels of phosphorylated AKT in glioma cells. The AKT signaling activator SC79 partly attenuated the inhibitory effects of ACTL6A shRNA on glioma cell migration. Additionally, the knockdown of ACTL6A enhanced the sensitivity of glioma cells to TMZ. In conclusion, these results suggest that ACTL6A knockdown inhibited the migration of human glioma cells, at least in part through inactivation of the AKT signaling pathway, and increased the sensitivity of glioma cells to TMZ. Therefore, ACTL6A may be a potential therapeutic target for glioma.

GALNT6 Knockdown Inhibits the Proliferation and Migration of Colorectal Cancer Cells and Increases the Sensitivity of Cancer Cells to 5-FU.

The incidence of colorectal cancer (CRC) is increasing annually worldwide, highlighting the need for novel therapeutics to be developed. GALNT6 is a member of the N-acetylgalactosyltransferase enzyme family, which exhibits oncogenic functions in several types of cancers, such as breast cancer and ovarian cancer. However, the function of GALNT6 in CRC has not received much attention in recent years and is therefore poorly understood. In this study, the GALNT6 gene was screened using RNA-seq data obtained from The Cancer Genome Atlas (TCGA). RNA-seq data from 50 pairs of matched CRC patients in TCGA were obtained and analyzed, and the protein expression levels of GALNT6 were verified in 10 pairs of clinical samples. These samples showed that GALNT6 was highly expressed in CRC tissues. Functional analysis also showed that GALNT6 knockdown inhibited the proliferation and migration of CRC cells and increased the number of apoptotic cells. Furthermore, GALNT6 knockdown suppressed tumor growth in vivo. GALNT6 also regulated the AKT pathway based on ingenuity pathway analysis and western blotting assay. Finally, GALNT6 knockdown was observed to increase the sensitivity of CRC cells to 5-Fluorouracil (5-FU). These results, taken together, show that GALNT6 knockdown inhibits proliferation and migration of CRC cells and increases cellular sensitivity to 5-FU. It is therefore possible that targeting GALNT6 might prove to be an effective avenue for exploration in any attempt to develop new therapies for the treatment of CRC.

A seven-gene signature model predicts overall survival in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a potentially fatal urogenital disease. It is a major cause of renal cell carcinoma and is often associated with late diagnosis and poor treatment outcomes. More evidence is emerging that genetic models can be used to predict the prognosis of KIRC. This study aimed to develop a model for predicting the overall survival of KIRC patients. RESULTS: We identified 333 differentially expressed genes (DEGs) between KIRC and normal tissues from the Gene Expression Omnibus (GEO) database. We randomly divided 591 cases from The Cancer Genome Atlas (TCGA) into training and internal testing sets. In the training set, we used univariate Cox regression analysis to retrieve the survival-related DEGs and futher used multivariate Cox regression with the LASSO penalty to identify potential prognostic genes. A seven-gene signature was identified that included APOLD1, C9orf66, G6PC, PPP1R1A, CNN1G, TIMP1, and TUBB2B. The seven-gene signature was evaluated in the training set, internal testing set, and external validation using data from the ICGC database. The Kaplan-Meier analysis showed that the high risk group had a significantly shorter overall survival time than the low risk group in the training, testing, and ICGC datasets. ROC analysis showed that the model had a high performance with an AUC of 0.738 in the training set, 0.706 in the internal testing set, and 0.656 in the ICGC external validation set. CONCLUSION: Our findings show that a seven-gene signature can serve as an independent biomarker for predicting prognosis in KIRC patients.

Lnc GNG12-AS1 knockdown suppresses glioma progression through the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly being regarded as regulators of glioma development. Notably, some studies report that GNG12-AS1 plays important functions and molecular mechanism in breast cancer, but there are no existing studies in glioma. OBJECTIVE: To analyze the biological functions and potential mechanisms of GNG12-AS1 in glioma. METHODS: We detected the expression of GNG12-AS1 in glioma tissues through analyzing TCGA data as well as our clinical samples. We then evaluated cell proliferation through MTT assay and colony formation and cell migration by transwell assay, wound healing assay and single cell tracking assay. After, we analyzed the effects of the AKT/GSK-3ß/ß-catenin through Western blotting and utilized the ß-catenin agonist SKL2001 for the rescue experiment. RESULTS: GNG12-AS1 was highly expressed in glioma tissues. The silence of GNG12-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition of glioma cells, and reduced the activity of the AKT/GSK-3ß/ß-catenin pathway. Notably, SKL2001 could reverse cell migration as well as ß-catenin expression in glioma cells with lower GNG12-AS1 expression. CONCLUSIONS: GNG12-AS1 regulates proliferation and migration of glioma cells through the AKT/GSK-3ß/ß-catenin signaling and can perhaps be a new target for the treatment of glioma.

Logistic regression analyses of factors affecting fertility of intrauterine adhesions patients.

BACKGROUND: Intrauterine adhesion (IUA) prevalence is difficult to measure, but appears to have increased over the last few decades. The reproductive outcomes following hysteroscopic adhesiolysis (HA) for moderate-severe IUAs were unsatisfactory, and few studies have analyzed the clinical characteristics pre-, intra- and post-HA to determine the main risk factors for infertility in patients with IUAs. METHODS: This retrospective observational study included 406 patients, desiring fertility, who had undergone HA between January 1st, 2016 to May 31st, 2017, and had moderate-to-severe IUA [5-12 on the American Fertility Society (AFS) classification scale]. Logistic regression was performed to analyze the data of the clinical characteristics associated with IUA. RESULTS: A total of 406 IUA patients were initially collected. Twenty-six [26] were lost during follow-up or excluded by other criteria; 380 were included in the study with a follow-up period ranging from 2 to 3 years. There were 215 patients (56.6%) that became pregnant, of whom 18 spontaneously miscarried, 5 birthed prematurely (31-36 gestational weeks), 182 delivered at term, and 10 were pregnant at the end of the study. A bivariate and binary logistic regression analysis showed that an age of >30 years, cohesive IUA, lack of increased menstrual volume, and more than 2 times undergoing HA procedure were the risk factors for infertility in IUA patients (P<0.05). CONCLUSIONS: Age, severity of IUA, increased menstrual volume, and HA procedures were the dominant factors affecting reproductive outcomes and may be regarded as potential predictors for evaluating IUA prognosis.

Study on the correlation among dysbacteriosis, imbalance of cytokine and the formation of intrauterine adhesion.

BACKGROUND: Intrauterine adhesion (IUA) is one of the most important causes of female infertility, while iatrogenic endometrial injury is the main, but not the entire, cause of IUA. The microorganisms of the female reproductive tract play an important role in its health and disease. The imbalance of immune regulation caused by the imbalance of reproductive tract dysbacteriosis may be an important link in the formation mechanism of uterine cavity adhesion. METHODS: We prospectively enrolled 30 patients diagnosed with IUA and 30 women with a history of intrauterine surgery, but without IUA, as control subjects. All participants were diagnosed with hysteroscopy while two swabs-one being leucorrhea drawn from the middle of the vagina and the other being cervical mucus drawn from the cervical canal-were taken. The bacterial load and community were identified by 16S rDNA quantitative polymerase chain reaction and pyrosequencing. Immunocytokines in serum were quantitatively detected by human T-helper cytokine kit. The correlation between Th cytokines and microorganisms in IUA and non-IUA groups was analyzed. RESULTS: Compared with non-IUA participants at the phylum level, patients with IUA had a significantly higher percentage of firmicutes in most samples, while the diversity of bacteria was significantly decreased. Some species that were members of vaginal and cervical canal bacterial phyla, including Euryarchaeota, Acidobacteria, Chlamydiae, Chlorobi, Planctomycetes and TM6 (Dependentiae), almost disappeared. The quantity in serum of IUA patients of classical proinflammatory cytokines IL-6 and TNF-γ, released from immune cells, also known as profibrotic cytokines, were significantly higher than that of the non-IUA women in our study (P<0.05). CONCLUSIONS: IUA is characterized by an increased bacterial burden, decreased diversity of bacterial communities in the vagina/cervical canal, and increased immune cytokines of pro-fibrosis, which may predict new and more effective therapeutic schemes for the treatment of IUA.

Growth hormone promotes human endometrial glandular cells proliferation and motion through the GHR-STAT3/5 pathway.

BACKGROUND: This study aims at investigating the effect of growth hormone (GH) on the growth of human endometrial glandular cells (hEGCs) and preliminary exploring its mechanism. METHODS: HEGCs were isolated from the endometrial biopsies and exposed to different dose of GH (0, 50, 100, and 200 ng/mL). Cell proliferation and cell cycle assay, migration assay was performed to investigate the growth and motivation of hEGCs, respectively. Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry (ICC), and western blot (WB) were processed to investigate its related gene or protein expression. RESULTS: The results revealed that GH administration promoted the proliferation, cell cycle, migration, and growth hormone receptors (GHRs) expression of the hEGC. We further inhibited GHRs with AG490, and the inhibitor reversed the effects of GH on cell growth, motion, and the activation of GHR and STAT3/5. CONCLUSIONS: GH promoted hEGCs proliferation and motion, which is GHR-JAK-STAT3/5 signaling pathway-dependent. These findings reveal the essential roles of GH in the hEGCs growth and provide evidence for potential GH therapy in intrauterine adhesion (IUA) treatment.