Endometriosis is a common and benign gynecological disorder but exhibits malignant features. However, the underlying pathogenesis and pathophysiology of endometriosis remain unclear. Circular RNAs have been demonstrated to participate in the occurrence and progression of multiple diseases. This study was aimed to explore the roles of circATRNL1 in endometriosis in vitro. Based on the results of reverse transcription-quantitative polymerase chain reaction analysis, we found significant upregulation of circATRNL1 and Yes-associated protein 1 (YAP1), while downregulation of miR-141-3p and miR-200a-3p in ectopic tissues compared to eutopic tissues. The immunohistochemistry and western blot analysis showed differentially expressed epithelial–mesenchymal transition (EMT) markers between EuEM and EcEM tissues. The in vitro assays indicated that overexpression of circATRNL1 could promote the proliferation, migration, and invasion of Ishikawa cells, and induce EMT process, while circATRNL1 silencing showed the opposite effect. The mechanical investigation indicated that circATRNL1 upregulated YAP1 by sponging miR-141-3p and miR-200a-3p. Gain-of-function assays validated the inhibitory function of miR-141-3p and miR-200a-3p in endometriosis. The results of rescue assays confirmed the function of circATRNL1–miR-141-3p/miR-200a-3p–YAP1 axis on Ishikawa cells. Our findings demonstrate that abnormal upregulation of circATRNL1 regulates cell proliferation and motility and promotes EMT process via the miR-141-3p/miR-200a-3p–YAP1 axis in vitro, which could contribute to the progression of endometriosis.

Fat mass and obesity-associated protein (FTO) regulates critical pathways in various diseases, including malignant tumours. However, the functional link between FTO and its target genes in epithelial ovarian cancer (EOC) development remains to be elucidated. In this study, the biological functions of FTO were verified in vitro and in vivo. The m6A modification and the binding sites of SNAI1 mRNA were confirmed by m6A RNA immunoprecipitation (MeRIP) and RIP experiments. The actinomycin D assay was used to test the stability of RNA. We found that FTO was downregulated with increased m6A levels in EOC. Reduced expression of FTO was associated with a higher FIGO stage in patients with EOC. Mechanistically, FTO decreased the m6A level and stability of SNAI1 mRNA, causing downregulation of SNAI1 and inhibiting epithelial–mesenchymal transition (EMT). Furthermore, FTO-mediated downregulation of SNAI1 expression depended on IGF2BP2, which acted as an m6A reader binding to the 3′ UTR region of SNAI1 mRNA to promote its stability. In conclusion, FTO inhibits SNAI1 expression to attenuate the growth and metastasis of EOC cells in an m6A-IGF2BP2-dependent manner. Our findings suggest that the FTO-IGF2BP2-SNAI1 axis is a potential therapeutic target in EOC.

There is a pressing need for innovative therapeutic strategies for patients with epithelial ovarian cancer (EOC). Previous studies have shown that UNC-51-like kinase 1 (ULK1), a serine/threonine kinase, is crucial in regulating cellular autophagy and mitophagy across various tumor types. However, the clinical implications, biological functions, and potential mechanisms of ULK1 in EOC remain poorly understood. This study demonstrates that ULK1 expression is upregulated in EOC tissue samples and EOC cell lines, with increased ULK1 expression correlating with poor prognosis. Functionally, overexpressed ULK1 enhances the proliferation and migration abilities of EOC cells both in vitro and in vivo. Mechanistically, ULK1 was identified as an m6A target of WTAP. WTAP-mediated m6A modification of ULK1 enhanced its mRNA stability in an IGF2BP3-dependent manner, leading to elevated ULK1 expression and enhanced mitophagy in EOC. In summary, our research reveals that the WTAP/IGF2BP3-ULK1 axis significantly influences protective mitophagy in EOC, contributing to its progression. Therefore, the regulatory mechanisms and biological function of ULK1 identify it as a potential molecular target for therapeutic intervention in EOC.

Background: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications. Case presentation: A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (β-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum β-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum β-hCG returned to normal range on the 23^th postoperative day. Conclusions: Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.

Background: Circular RNAs (circRNAs) with miRNA response elements (MREs) could function as competing endogenous RNA (ceRNA) in regulating gene expression, thus playing vital roles in pathogenesis and progression of many diseases. However, the function of circRNAs in endometriosis remains unknown. This study was carried to profile the expression patterns of circRNAs in ovarian endometriosis.Methods: High throughput RNA‐Seq was performed in six paired ectopic and eutopic endometrium tissues (ecEM vs. euEM), followed by quantitative real‐time polymerase chain reaction (qRT‐PCR) in 30 paired samples. Through bioinformatics prediction, we constructed a circRNA‐miRNA ‐mRNA network and elucidated circRNAs functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.Results: A total of 146 upregulated and 148 downregulated circRNAs were identified, binding with 2,495 MREs. The qRT‐PCR validation results of four upregulated circRNAs matched the RNA‐Seq data. The ceRNA network included 48 miRNAs and 296 mRNAs. Functional analysis revealed several important pathways such as MAPK signaling pathway, and PI3K‐AKT signaling pathway, which might be associated with the pathogenesis and development of endometriosis.Conclusion: Our data suggested that circRNAs are differentially expressed in endometriosis, which might be candidate factors for pathogenesis of this disease and be considered as promising therapeutic targets in the future.

Background: While caudal block has been widely used during pediatric lower limbs and lower abdominal surgeries, few studies to date have evaluated the perioperative effects of caudal block on pediatric patients in laparoscopic upper urinary tract surgery. Methods: Ninety-six pediatric patients, aged 6 months to 7 years, ASA grade I-II, scheduled to undergo laparoscopic upper urinary tract surgery, were randomized to a non-block group (no caudal block performed), an ROP1.0 group (patients received 1.0 mL/kg of 0.15% ropivacaine) and an ROP1.3 group (patients received 1.3 mL/kg of 0.15% ropivacaine). The primary outcome variable was perioperative fentanyl use. The secondary outcome variables were pain score, hemodynamic fluctuation, the number of patients needing rescue fentanyl and side effects. Results: Caudal block with 1.3 mL/kg of 0.15% ropivacaine significantly decreased perioperative fentanyl usage (ROP 1.3 vs. non-caudal block, P < 0.01; ROP 1.3 vs. ROP 1.0, P < 0.05). Moreover, patients in the ROP1.3 group, compared to those without, displayed more stable hemodynamics, lower pain score in the PACU and 8 h after operation, less demand for rescue fentanyl, shorter time of PACU stay. Conclusions: Caudal block with 1.3 mL/kg of 0.15% ropivacaine reduced perioperative fentanyl use during laparoscopic upper urinary tract surgery on pediatric patients and produced good postoperative analgesia when compared with no caudal block and caudal block with 1.0 mL/kg of 0.15% ropivacaine. Trial registration: Clinical trial number: ChiCTR1800015549, chictr.org.cn.