Identification of diagnostic biomarkers in patients with gestational diabetes mellitus based on transcriptome gene expression and methylation correlation analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high prevalence in the period of pregnancy. However, the lack of gold standards in current screening and diagnostic methods posed the biggest limitation. Regulation of gene expression caused by DNA methylation plays an important role in metabolic diseases. In this study, we aimed to screen GDM diagnostic markers, and establish a diagnostic model for predicting GDM. METHODS: First, we acquired data of DNA methylation and gene expression in GDM samples (N = 41) and normal samples (N = 41) from the Gene Expression Omnibus (GEO) database. After pre-processing the data, linear models were used to identify differentially expressed genes (DEGs). Then we performed pathway enrichment analysis to extract relationships among genes from pathways, construct pathway networks, and further analyzed the relationship between gene expression and methylation of promoter regions. We screened for genes which are significantly negatively correlated with methylation and established mRNA-mRNA-CpGs network. The network topology was further analyzed to screen hub genes which were recognized as robust GDM biomarkers. Finally, the samples were randomly divided into training set (N = 28) and internal verification set (N = 27), and the support vector machine (SVM) ten-fold cross-validation method was used to establish a diagnostic classifier, which verified on internal and external data sets. RESULTS: In this study, we identified 465 significant DEGs. Functional enrichment analysis revealed that these genes were associated with Type I diabetes mellitus and immunization. And we constructed an interactional network including 1091 genes by using the regulatory relationships of all 30 enriched pathways. 184 epigenetics regulated genes were screened by analyzing the relationship between gene expression and promoter regions' methylation in the network. Moreover, the accuracy rate in the training data set was increased up to 96.3, and 82.1% in the internal validation set, and 97.3% in external validation data sets after establishing diagnostic classifiers which were performed by analyzing the gene expression profiles of obtained 10 hub genes from this network, combined with SVM. CONCLUSIONS: This study provided new features for the diagnosis of GDM and may contribute to the diagnosis and personalized treatment of GDM.

MicroRNA-2861 targets STAT3 and MMP2 to regulate the proliferation and apoptosis of ectopic endometrial cells in endometriosis.

This study aimed to elucidate the roles and regulatory mechanism of miR-2861 in the development of endometriosis. The expression of miR-2861 in endometriotic tissues and eutopic endometrial tissues was determined. Ectopic endometrial cells were transfected with miR-2861 mimic, miR-2861 inhibitor and their corresponding controls. The effects of miR-2861 overexpression and inhibition on cell proliferation and apoptosis were then investigated. In addition, regulatory relationship between miR-2681 and signal transducer and activator of transcription 3 (STAT3) or matrix metalloproteinase 2 (MMP2) was explored, as well as between STAT3 and MMP2. Compared with eutopic endometrial tissues, miR-2861 was significantly downregulated in endometriotic tissues. Overexpression of miR-2861 markedly inhibited ectopic endometrial cell proliferation and induced apoptosis. Additionally, STAT3 and MMP2 were confirmed as the targets of miR-2861, and the effects of knockdown of STAT3 or MMP2on regulating cell proliferation and apoptosis were opposite with inhibition of miR-2861. Besides, STAT3 could enhance the expression of MMP2 in ectopic endometrial cells. Our study reveals that miR-2861 was lowly expressed in endometriotic tissues, and downregulation of miR-2861 may promote proliferation and inhibit apoptosis of ectopic endometrial cells in endometriosis via upregulation of STAT3 and MMP2. miR-2861 may be a potential biomarker or therapeutic target for endometriosis.

Fertility performance and the predictive value of the endometriosis fertility index staging system in women with recurrent endometriosis: A retrospective study.

This study presents the postoperative pregnancy rate of women with recurrent endometriosis and evaluates the predictive value of the endometriosis fertility index (EFI) for the pregnancy.A total of 107 women who wished to conceive after surgery for recurrent endometriosis from January 2007 to December 2016 were included. The EFI score was calculated postoperatively. The receiver operator characteristic (ROC) curve was plotted to determine the most promising contributor to predicting pregnancy, and Kaplan-Meier (K-M) analysis was used to estimate the cumulative pregnancy rate (CPR).A total of 61 pregnancies were registered in 58 women and the remaining 49 patients failed to become pregnant. The EFI score was strongly associated with the postoperative fertility prognosis. The CPRs during the first 2 and 3 years postoperatively were 51.86% and 66.38%, respectively, and increased to 71.98% within the first 5 years postoperatively in patients with EFI scores ≥5. However, the CPR was 26.00% during the first 2 years after surgery in individuals with EFI scores <5, and there was no increase in the CRP thereafter.Women suffering from recurrent endometriosis still experienced a probability of natural pregnancy, especially patients with EFI scores ≥5. The EFI score had good predictive power for postoperative pregnancy in these patients.

Exosomal long non-coding RNAs: biological properties and therapeutic potential in cancer treatment.

Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.

Staged microvascular anastomosis training program for novices: transplantation of both kidneys from one rat donor.

BACKGROUND: Rat renal transplantation is an essential experimental model and requires greater microsurgical skills. Thus, training novices to perform quick and reliable microvascular anastomosis is of vital importance for rat renal transplantation. In this study, we developed and evaluated a staged microvascular anastomosis training program for novices, harvesting and transplanting both kidneys from one rat donor. METHODS: Five trainees without any prior microsurgical experience underwent a training program in which the goals were staged according to difficulty. Each trainee had to achieve satisfactory results as evaluated by a mentor before entering the next stage. Rat renal transplantation was accomplished by end-to-end technique with a bladder patch. In the intensive rat renal transplantation stage, the trainees required an average of 20 independent attempts at isotransplantation as final training assessment. RESULTS: After 2 months of intensive practice, all trainees had achieved stable and reproducible rat renal transplantation, with a satisfactory survival rate of 85.9% at postoperative Day 7. The total mean operative time was 78.0 minutes and the mean hot ischemia time was 26.2 minutes. With experience increasing, the operative time for each trainee showed a decreasing trend, from 90-100 minutes to 60-70 minutes. After 20 cases, the mean operative time of the trainees was not statistically significantly different from that of the mentor. CONCLUSION: Harvesting and transplanting both kidneys from one rat donor after a staged microvascular anastomosis training program is feasible for novices without any prior microsurgical skills.

Pure natural orifice translumenal endoscopic surgery management of simple renal cysts: 2-year follow-up results.

BACKGROUND AND PURPOSE: Retrograde ureteroscopic marsupialization is a pure natural orifice translumenal endoscopic surgery (NOTES). We retrospectively examined the feasibility and safety of this technique to manage symptomatic simple renal cysts. PATIENTS AND METHODS: Sixteen patients with simple renal cysts were selected and treated by incising the cyst wall to drain into the collecting system through retrograde ureteroscopy. A retrospective observational study was performed to evaluate the patient's symptomatic and radiologic results after ureteroscopic marsupialization. Symptomatic success based on pain relief was evaluated using a visual analog pain scale preoperatively and postoperatively. Radiologic success was defined as no recurrence of the cyst or a reduction in cyst size by at least half. RESULTS: There were no intraoperative or postoperative complications observed. The mean operative time was 35 minutes (range 20-50 min). The mean hospital stay was 3.4 days (range 2-5 d). Of the 16 patients, one patient was lost at follow-up. The symptoms based on pain had resolved in 13 (83%) cases but remained in 2 cases at a mean follow-up of 24.2 months (range 6-36 mos). The average visual analog pain scale decreased from 6.7 (range 4-9) to 1.1 (range 0-5) at the sixth month. The mean size of all cysts decreased from 6.8 cm (range 4-10 cm) to 1.3 cm (range 0-5 cm). Radiographic success was achieved in 93% (14/15) of patients. Cytology and cyst wall pathology reports revealed no evidence of malignancy. CONCLUSIONS: Retrograde ureteroscopic marsupialization is a complete transurethral NOTES marsupialization. With appropriate patient selection, the minimally invasive retrograde ureteroscopic marsupialization is feasible, safe, and effective. It can be preferred to more invasive laparoscopic or open surgical approaches.

The mechanism of vacuum constriction devices in penile erection: the NO/cGMP signaling pathway?

The traditional theories believe that vacuum constriction devices (VCD) is the mechanism through a suction chamber promoting penile blood engorgement and maintaining tumescence with a constriction band. For that mechanical nature of the device, many authors and patients consider the devices are passive engorgement, lack of spontaneous erections, and only rely on the constriction bands to prevent venous outflow to maintain the erection. However, recent clinical studies show that many patients using the VCD devices without the constriction band, but still maintain the erections and return to natural erections. The current theories cannot explain this phenomenon. We think that the VCD devices not only through the mechanical nature to prevent venous outflow by the constriction bands to maintain the erection, but also through the suction chamber to stretch and stimulate the corpora cavernosa nerves, muscles, and blood vessels, and led to the neurotransmitter nitric oxide (NO) released. NO as the principal messenger molecule though the NO/cGMP signaling pathway to mediate corporal smooth muscle relaxation and penile erection. The relaxation of corporal smooth muscle creates pressure in the tunica albuginea can prevent venous outflow and maintain erection. This can explains the phenomenon of many patients using the VCD devices without the constriction bands also maintain the erections and return to natural erections. Thus, we put forward the hypothesis that the classical NO/cGMP signaling pathway is also involved in the penile erections when using the VCD devices. In the future, we could design and apply rat-specific VCD devices without the constriction bands in rat model to analyze the cell and molecular changes in rat corpora cavernosa to test this hypothesis.