CXCL10-based gene cluster model serves as a potential diagnostic biomarker for premature ovarian failure.

Objective: Premature ovarian failure (POF) is a disease with high clinical heterogeneity. Subsequently, its diagnosis is challenging. CXCL10 which is a small signaling protein involved in immune response and inflammation may have diagnostic potential in detection of premature ovarian insufficiency. Therefore, this study aimed to investigate CXCL10 based diagnostic biomarkers for POF. Methods: Transcriptome data for POF was obtained from the Gene Expression Omnibus (GEO) database (GSE39501). Principal component analysis (PCA) assessed CXCL10 expression in patients with POF. The receiver operating characteristic (ROC) curve, analyzed using PlotROC, demonstrated the diagnostic potential of CXCL10 and CXCL10-based models for POF. Differentially expressed genes (DEGs) in the control group of POF were identified using DEbylimma. PlotVenn was used to determine the overlap between the POF-control group and the high-/low-expression CXCL10 groups. QuadrantPlot was employed to detect CXCL10-dysregulated genes in POF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted on DEGs using RunMulti Group cluster Profiler. A POF model was induced with cisplatin (DDP) using KGN cells. RT-qPCR and Western blot were used to measure the expression of CXCL10, apoptosis-related proteins, and peroxisome proliferator-activated receptor (PPAR) signaling pathway-related proteins in this model, following siRNA-mediated silencing of CXCL10. Flow cytometry was employed to assess the apoptosis of KGN cells after CXCL10 downregulation. Results: The expression of CXCL10 is dysregulated in POF, and it shows promising diagnostic potential for POF, as evidenced by an area under the curve value of 1. In POF, we found 3,362 up-regulated and 3,969 down-regulated DEGs compared to healthy controls, while the high- and low-expression groups of POF (comprising samples above and below the median CXCL10 expression) exhibited 1,304 up-regulated and 1,315 down-regulated DEGs. Among these, 786 DEGs consistently displayed dysregulation in POF due to CXCL10 influence. Enrichment analysis indicated that the PPAR signaling pathway was activated by CXCL10 in POF. The CXCL10-based model (including CXCL10, Itga2, and Raf1) holds potential as a diagnostic biomarker for POF. Additionally, in the DDP-induced KGN cell model, interfering with CXCL10 expression promoted the secretion of estradiol, and reduced apoptosis. Furthermore, CXCL10 silencing led to decreased expression levels of PPARß and long-chain acyl-CoA synthetase 1 compared to the Si-NC group. These results suggest that CXCL10 influences the progression of POF through the PPAR signaling pathway. Conclusion: The CXCL10-based model, demonstrating perfect diagnostic accuracy for POF and comprising CXCL10, Itga2, and Raf1, holds potential as a valuable diagnostic biomarker. Thus, the expression levels of these genes may collectively provide valuable diagnostic information for POF.

[Retracted] Inhibition of microRNA­19b promotes ovarian granulosa cell proliferation by targeting IGF­1 in polycystic ovary syndrome.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data (or portions of the data thereof) shown in Figs. 2C and 5G were strikingly similar to data that had appeared in different form in other articles by different authors at different research institutes. Owing to a general lack of confidence in the presented data, and due to the fact that the contentious data in the above article may have already been published, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4889­4898, 2018; DOI: 10.3892/mmr.2018.8463].

Application of laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration in type III cesarean scar pregnancy.

To investigate the efficacy and safety of laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration in type III cesarean scar pregnancy. 135 cases of cesarean scar pregnancy in Guangzhou Women and Children's Hospital from November 2017 to November 2020 were collected and 32 cases of type III patients were retrospectively analyzed. They were divided into internal iliac artery temporary occlusion (IIATO) group (21 cases), and bilateral uterine artery embolization (UAE) group (11 cases). The general condition, intraoperative bleeding, postoperative complications, and prognosis of the two groups were analyzed. In the IIATO group, the bilateral internal iliac arteries were temporarily blocked with No. 10 silk thread under laparoscopy. The scar pregnancy clearance and repair of the scar were performed after incision. Subsequently, we performed hysteroscopic aspiration. After the operation, the internal iliac artery ligation thread was removed. In the UAE group, the patients were treated with bilateral uterine artery embolization. Laparoscopic uterine scar repair and hysteroscopy aspiration were performed within 24 hours after embolization. There was no significant difference in age, times of pregnancy, times of cesarean section and gestational weeks between the two groups (P>0.05). No significant differences were observed in the diameter of gestational sac or gestational mass and serum human chorionic gonadotropin (ß-hCG) level between the two groups before operation (P>0.05). The operations were successfully completed in 32 patients, and intraoperative blood loss was 67.14±32.78 ml and 71.35±31.56 ml, respectively (P<0.05). The length of hospital stay was 5.14±0.32 day and 4.97±0.21 day, respectively. No peri-procedural bleeding occurred and no secondary surgeries were required. Laparoscopic internal iliac artery temporary occlusion and uterine repair combined with hysteroscopic aspiration is an effective and safe treatment for type III cesarean scar pregnancy, with less postoperative complications and better protection of fertility function for patients.

Copy Number Variation Analysis of Euploid Pregnancy Loss.

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death. Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1.10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12.0. Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs. Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss.

Diagnosis of Interventional Transvaginal Maternal Diseases Based on Color Doppler Ultrasound.

In recent years, with the development of color Doppler ultrasound technology in obstetrics, this noninvasive, direct, convenient, and sensitive inspection method has become one of the best methods to observe the fetal circulation in the uterus. This paper discusses the clinical value of using transvaginal color Doppler ultrasound in the differential diagnosis of ovarian corpus luteum disease and ectopic pregnancy disease. This paper selects 100 cases of ectopic pregnancy and 100 cases of pregnant corpus luteum as the experimental research objects. Clinical analysis of transvaginal color Doppler ultrasonography was performed on all patients. In the process of measuring the patient's ectopic pregnancy, the size of the patient's adnexal mass is mainly measured, and the blood flow spectrum is measured. The clinical choice of transvaginal color Doppler ultrasound method to distinguish ectopic pregnancy disease and corpus luteum pregnancy disease can play a significant value. It can be effectively diagnosed according to the type of disease, then effective methods can be studied for clinical treatment, the quality of life of patients with the two diseases can be significantly improved, and the clinical application value of color Doppler ultrasound can be improved.

Outcome of Gynecologic Laparoendoscopic Single-Site Surgery with a Homemade Device and Conventional Laparoscopic Instruments in a Chinese Teaching Hospital.

OBJECTIVE: To demonstrate various benign gynecologic diseases that can be performed by laparoendoscopic single-site surgery (LESS) with conventional laparoscopic instruments. METHOD: Patients with benign gynecologic diseases that need ovarian cystectomy, fallopian tube resection, or myomectomy were divided into experimental group and control group, and perioperative outcomes of these patients were analyzed. RESULTS: From November 2017 to May 2018, 65 LESS gynecological surgeries were performed, among which there were 25 ovarian cystectomies, 28 unilateral fallopian tube resections, and 12 myomectomies. All the surgeries were completed smoothly, and only one surgery needed one more additional port. No patients have severe complications. Operative time, intraoperative blood loss, and perioperative complications have no difference between the two groups. The LESS laparoscopy group had less postoperative pain scores and longer bowel recovering time, compared with the conventional laparoscopy group (<0.05). CONCLUSION: Compared with traditional laparoscopy, LESS surgery with conventional laparoscopic instruments is feasible and safe, but postoperative exhaust time is longer than the control group.

Molecular mechanisms involved in TGF-ß1-induced Muscle-derived stem cells differentiation to smooth muscle cells.

We investigated the molecular mechanisms involved in transforming growth factor beta 1 (TGF-ß1)-induced myogenic stem cell differentiation to smooth muscle cells. We isolated muscle-derived stem cells (MDSCs) from gastrocnemius muscles following their identification by immunohistochemistry analysis of desmin and flow cytometry analysis of SCA-1, CD34, and CD45. MDSCs at passage 3 (PP3) were cultured in vitro to examine the effects of MDSC induction. Gene ontology and KEGG pathway analyses were performed to analyze these differentially expressed genes. Reduced representation bisulfite sequencing was performed in TGF-ß1-treated and untreated cells to evaluate differences in the methylation status and analyze the chromosomal distribution of differentially methylated sites (DMSs). Significant morphological changes to cells were observed at PP3, and most PP3 cells were positive for desmin and SCA-1, and were confirmed to be MDSCs. Results of western blot and immunohistochemistry analyses suggested that expressions of a-SMA and CNN1 significantly increased after treatment with TGF-ß1. Global transcriptome analysis identified 1996 differentially expressed genes (MSC_TGFß1/MSC_NC). Results of methylome analysis indicated that there were more hypermethylation sites in the untreated group than in the TGF-ß1-treated group. Most DMSs were hypermethylated, whereas a small portion was hypomethylated. The chromosomal distribution of DMSs indicated that chromosome 1 had the highest proportion of DMSs, whereas the Y chromosome had the fewest DMSs. Sud2, Pcdh19, and Nat14 are potential core genes involved in cell differentiation. These results may explain the mechanisms of cell differentiation and provide useful information regarding diseases such as pelvic organ prolapse.

Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by targeting IGF-1 in polycystic ovary syndrome.

The purpose of the present study was to investigate the functional role of microRNA (miR)-19b in polycystic ovary syndrome (PCOS) and try to elucidate its underlying mechanisms. Expression of miR­19b and insulin­like growth factor 1 (IGF-1) was examined in ovarian cortexes [(from 18 women with PCOS and 10 who did not have PCOS (non­PCOS)] and KGN cells. Cell proliferation assays (cell viability and colony formation assay) were performed following overexpression or inhibition of miR­19b and IGF­1 or following insulin treatment in KGN cells. Expression levels of the cell cycle-associated protein cyclin D1 and cyclin­dependent kinase (CDK) 1 were analyzed following overexpression or inhibition of miR-19b and IGF-1. Potential miR­19b targets were identified by bioinformatics. Luciferase assay, reverse transcription­quantitative polymerase chain reaction and western blotting were performed to determine whether IGF­1 was a target of miR­19b. miR­19b expression was significantly decreased in the PCOS ovarian cortex and KGN cells and its identified target, IGF­1, was upregulated. miR­19b overexpression inhibited cell proliferation at G2/M phrase. Overexpression of IGF­1 promoted cell viability and colony formation ability in KGN cells. The expression of cyclin D1 and CDK1 was statistically increased by inhibition of miR­19b and overexpression of IGF­1. High concentrations of insulin decreased levels of miR­19b, stimulated KGN cell proliferation, and elevated IGF­1 levels. Inhibition of miR­19b promoted ovarian granulosa cell proliferation by targeting IGF­1 in PCOS. Insulin decreased the expression levels of miR­19b and stimulated cell proliferation. The present study suggested that overexpression of miR­19b may be a potential therapeutic approach for PCOS.