Self-esteem, depression, anxiety and sexual function in Mayer-Rokitansky-Küster-Hauser syndrome with neovagina: A case series.

BACKGROUND: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare condition with significant psychological implications. However, our understanding of its impact on postoperative sexual function and mental health is still limited. AIM: Evaluate the mental health status and sexual functioning of women with MRKH syndrome after vaginoplasty surgery. METHODS: We enrolled 53 cases with MRKH syndrome who underwent artificial vaginoplasty. The participants were asked to participate in a two-round survey conducted between February 2021 during the covid-19 period and March 2023. The survey included questionnaires to measure depression, anxiety, self-esteem, and sexual functioning. Differences between scores over time were analysed using a paired sample t-test, and we assessed the correlation between mental health and sexual functioning. RESULTS: In the first round, patients' mean ± SD age at surgery was 23.6 ± 4.5 years old, and the mean ± SD time that had elapsed since surgery at the time of the survey was 34.2 ± 20.8 months. None of the patients reported low self-esteem, 45.3 % reported mild-to-moderate depression, and 34.0 % reported mild anxiety. Thirty patients have had vaginal intercourse during the last six months. The mean ± SD Female Sexual Functioning Index score was 24.6 ± 4.4, and 60.0 % had a score of 23.5 or higher, indicating high sexual functioning. The sexual functioning scores were positively correlated with self-esteem scores and negatively correlated with depression or anxiety scores (p < 0.05). There was no significant improvement in patient's mental health status and sexual function between the second round survey (71.3 ± 17.8 months after surgery) and the first round survey (p > 0.05). In contrast, the sexual arousal of FSFI were significantly higher in the second survey round (p < 0.05). CONCLUSION: Most patients undergoing vaginoplasty reported persisting mental health challenges. However, the majority reported good sexual functioning.

Accumulation of dysfunctional tumor-infiltrating PD-1+ DCs links PD-1/PD-L1 blockade immunotherapeutic response in cervical cancer.

Various predictive biomarkers are needed to select candidates for optimal and individualized treatments. Tumor-infiltrating immune cells have gained increasing interest in cancer research for the prediction of therapeutic response and survival. However, the role of dendritic cells (DCs) in PD-1 blockade immunotherapy remains unclear. In this study, we identified a population of PD-1+ DCs in the tumor microenvironment (TME) of cervical cancer (CC). The accumulation of PD-1+ DCs in cervical tumors was correlated with advanced stages, elevated preoperative squamous cell carcinoma antigen levels and lymph-vascular space invasion. PD-1 expression was induced on activated tumor-associated DCs (TADCs) in vitro compared with their resting counterparts. This PD-1+ DC population was characterized by reduced secretion of cytokines (IL-12, TNF-α, and IL-1ß) and dysfunctional induction of T cell proliferation and cytotoxic reaction. PD-1 blockade significantly reinvigorated PD-1+ DCs to release IL-12, TNF-α, and IL-1ß compared with PD-1- DCs. TILs from samples with higher PD-1+ DC infiltration could be induced to achieve a greater killing effect of PD-1 blockade treatment. Our findings suggested a role for PD-1+ DCs in immune surveillance dysfunction and CC progression. PD-1+ DC density in the TME may serve as a diagnostic factor for predicting the optimal beneficiaries of PD-1/PD-L1 blockade immunotherapy in CC.

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis.

BACKGROUND: Although the tumorigenesis of cervical cancer (CC) has been widely investigated and recognized, the study of the systematic impact of histone deacetylase 10 (HDAC10), microRNA, and downstream molecular mechanisms in CC is still limited. Herein, cervical cancer, precancer lesions, and normal cervical tissues were collected to test the expression level of HDAC10, miR-223, and EPB41L3. The mechanism of HDAC10, miR-223, and EPB41L3 was interpreted in cervical cancer cells after HDAC10, miR-223, or EPB41L3 expression was altered. RESULTS: HDAC10 was poorly expressed in cervical cancer and precancer lesions, while miR-223 was highly expressed in cervical cancer. HDAC10 bound to miR-223, and miR-223 targeted EPB41L3. HDAC10 depressed the invasion property and tumorigenesis of cervical cancer via downregulating miR-223 and subsequently targeting EPB41L3. CONCLUSION: The study clarifies that HDAC10 inhibits cervical cancer by downregulating miR-223 and subsequently targeting EPB41L3 expression, which might provide a new insight for management upon cervical cancer and precancer lesions.

Diagnostic discrepancy between colposcopy and vaginoscopy: A case report.

BACKGROUND: Colposcopy currently plays a vital role in the diagnosis and treatment of lower genital diseases. Exposure and biopsy are two key steps in colposcopy. When the whole transformation zone or all lesions cannot be observed, we judge colposcopy as unsatisfactory. Unsatisfactory colposcopic examination may lead to the misdiagnosis of more severe diseases. The combination of colposcopy and vaginoscopy may contribute to accurate diagnosis and clinical decisions. CASE SUMMARY: Here, we introduce a case of posthysterectomy deep vaginal apex not fully exposed by colposcopy, and the biopsy result was a vaginal precancerous lesion. We adopted vaginoscopy to extend the observed area and expose the lesion thoroughly, and the biopsy result was vaginal squamous cancer. CONCLUSION: The patient received a precise diagnosis and early surgery due to the combination of colposcopy and vaginoscopy.

A ceRNA network of BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A shows prognostic value in cervical cancer.

OBJECTIVE: Cervical cancer (CC) ranks fourth most diagnosed cancer and cancer mortality in women. Long non-coding RNAs (lncRNAs) take important roles in CC development. This study aimed to identify more and novel competing endogenous RNA (ceRNA) mechanisms of lncRNAs in CC. MATERIALS AND METHODS: The miRNA expression dataset GSE20592 and lncRNA/mRNA expression dataset GSE63514 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DElncRNAs), and differentially expressed miRNAs (DEmiRNAs) between CC tumor and normal samples were identified with the criteria of adj.P.Value < 0.05 (Benjamini & Hochberg) and |log2(fold change)|>2. Functional enrichment analysis was performed for DEGs. The interaction pairs among lncRNAs, miRNAs and mRNAs were predicted and the ceRNA network was then constructed. Survival analysis was performed based on the TCGA dataset. RESULTS: Totally, 42 DEmiRNAs, 25 DElncRNAs, and 518 DEGs were identified in CC tumor samples versus normal tissues. The DEGs were associated with 'GO:0006260: DNA replication', 'GO:0051301: cell division', and 'hsa01100:Metabolic pathways'. The ceRNA network consisted of 878 lncRNA-miRNA-mRNA pairs. Of the miRNAs, lncRNAs, and genes with the top 10 interaction degrees in the ceRNA network, the upregulated cyclin dependent kinase inhibitor 2A gene (CDKN2A) was targeted by the downregulated DEmiRNAs including hsa-miR-125b-5p and hsa-miR-125a-5p, which were targeted by the upregulated DElncRNA BBOX1-AS1. The high expression level of CDKN2A contributed to the poor overall survival of patients with CC. CONCLUSIONS: The BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A ceRNA network is of great value in CC development.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.

Dysmenorrhea in patients with adenomyosis: A clinical and demographic study.

OBJECTIVE: To identify the risk factors associated with dysmenorrhea in adenomyosis and to discuss the potential hormone-based understanding of pain mechanisms. STUDY DESIGN: Adenomyosis patients with mild or no dysmenorrhea (n = 40, Group 1) and moderate-to-severe dysmenorrhea (n = 80, Group 2) were recruited. Charts of all patients were recorded. An immunohistochemistry (IHC) analysis was performed to detect the cellular levels of estrogen receptor-α (ER-α), estrogen receptor-ß (ER-ß), gonadotropin-releasing hormone receptor (GnRH-R), and neurofilaments (NFs) in 60 cases. RESULTS: A history of cesarean section (CS) was positively related to the degree of dysmenorrhea in adenomyosis (OR (95 % CI): 4.397 (1.371-14.104)). The ER-α levels in the eutopic endometrium (EUE) of Group 2 were higher than those in the ectopic endometrium (ECE) of Group 1. Group 2 had higher NF levels in the ECE than in the EUE. CONCLUSION: A history of CS is a risk factor for adenomyosis with moderate-to-severe dysmenorrhea. For patients with adenomyosis, high ER-α levels in the EUE and high NF levels in the ECE may be related to moderate-to-severe dysmenorrhea. These hormone-based mechanisms may contribute to our understanding of the pathogenesis of dysmenorrhea in adenomyosis.

Types and viral load of human papillomavirus, and vaginal microbiota in vaginal intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Human papilloma virus (HPV) infection is an important risk factor for vaginal intraepithelial neoplasia (VAIN). Recent studies have suggested that the microbiome may play a potential role in cervicovaginal diseases. This study aimed to explore the characteristics of the types and viral load of HPV in VAIN, as well as the association between vaginal microbiota and VAIN. METHODS: A total of 176 women, either with VAIN, or without VAIN but with HPV infection were enrolled in the study. Among them, 109 HPV positive cases were qualified for viral load assay. The vaginal microbiota of 122 HPV positive women, who were matched by severity of cervical lesions and menopause status, was determined by 16S ribosomal RNA (16S rRNA) sequencing. RESULTS: The top 5 types of HPV-associated vaginal lesions were HPV16 (24.2%), HPV52 (24.2%), HPV53 (16.1%), HPV58 (14.5%) and HPV66 (14.5%). The viral load of HPV types 16, 52, and 58 appeared higher in separate vaginal lesions than in histopathologically normal cases (P=0.026, 0.002, and 0.013, respectively). The vaginal microbiota of HPV-positive patients with VAIN did not exhibit a large change in diversity. Vaginal microbiota of VAIN was characterized by an increased abundance of Atopobium, Gardnerella, Allobaculum and Clostridium, as well as decreased abundance of Finegoldia, Actinobaculum and Blautia. A higher level of Enterococcus and some specific Clostridium spp. might be associated with an elevated risk of VAIN2/3. CONCLUSIONS: A higher level of viral load of HPV16, 52, and 58 may indicate VAIN. The composition of vaginal microbiota changes during the progression of VAIN and specific bacteria such as Atopobium, Gardnerella, Allobaculum, Enterococcus and Clostridium, may help to promote its development.

Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the ß-catenin signaling pathway.

BACKGROUND: The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. METHODS: A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. RESULTS: HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting ß-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. CONCLUSIONS: Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

Evaluation of a methylation classifier for predicting pre-cancer lesion among women with abnormal results between HPV16/18 and cytology.

BACKGROUND: Although HPV testing and cytology detection are successful for cervical screening in China, additional procedures are urgently required to avoid misdiagnosis and overtreatment. In this multicenter study, we collected cervical samples during screening in clinics. A total of 588 women with HPV16/18+ and/or cytology result ≥HSIL+ (high-grade squamous intraepithelial lesion or worse) were referred to colposcopy for pathological diagnosis. Methylation of S5 was quantified by pyrosequencing. RESULTS: The S5 classifier separates women with ≥HSIL+ from

Clinical outcomes of vaginectomy and laser ablation for the treatment of post-hysterectomy women with vaginal high-grade squamous intraepithelial lesions: A retrospective study.

OBJECTIVE: To evaluate the clinical outcomes of vaginectomy and laser ablation for the treatment of vaginal high-grade squamous intraepithelial lesion (HSIL) patients who underwent previous hysterectomy for cervical HSIL or cancer. STUDY DESIGN: The clinicopathologic data and follow-up information of 167 post-hysterectomy vaginal HSIL patients who underwent laser ablation or vaginectomy were retrospectively reviewed from 2010 to 2018 at the Obstetrics and Gynecology Hospital of Fudan University. RESULTS: Of the 167 vaginal HSIL patients enrolled, 74 patients underwent vaginectomy, and 93 patients underwent laser ablation. At a median follow-up of 15 months, 13 (7.8 %) patients experienced progression to vaginal cancer, and 22 (13.2 %) patients had persistent/recurrent disease. Upon multivariate analysis, laser ablation (OR: 5.16, p = 0.02), cytology indicating HSIL (OR: 25.45, p = 0.00), and a shorter interval between previous hysterectomy and vaginal HSIL diagnosis (< 24 vs ≥ 24 months, OR: 0.10, p = 0.02) were associated with disease persistence/recurrence. In post-hysterectomy for cervical HSIL patients, the vaginectomy group had a significantly higher recurrence-free survival rate (RFS, 94.5 % vs 69.0 %, p = 0.00) and a similar progression-free survival rate (PFS, 96.4 % vs 91.4 %, p = 0.17) compared with the laser ablation group. Among post-hysterectomy for cervical cancer patients, RFS (89.5 % vs 65.7 %, p = 0.04) and PFS (100.0 % vs 82.9 %, p = 0.05) were both higher in the vaginectomy group than in the laser ablation group. CONCLUSION: Compared with laser ablation, vaginectomy resulted in better clinical outcomes among vaginal HSIL patients who had undergone previous hysterectomy for cervical neoplasia.

Extracellular vesicle-mediated transfer of the lncRNA-TC0101441 promotes endometriosis migration/invasion.

Extracellular vesicular long noncoding RNAs (lncRNAs) to influence recipient cells is emerging as a novel mechanism for disease progression. TC0101441 is a newly identified metastasis-related lncRNA involved in cancer. Since endometriosis exhibits prometastasis behavior similar to those observed in cancer, we aimed to investigate whether TC0101441 is involved in endometriosis and, if so, whether extracellular vesicular TC0101441 contributes to the migration/invasion of endometriotic cyst stromal cells (ECSCs). Clinically, we found that TC0101441 was highly expressed in ectopic endometria than in the eutopic and normal endometria. Serum extracellular vesicular TC0101441 levels were substantially increased in patients at stage III/IV endometriosis in comparison with stage I/II endometriosis and controls. In vitro, using TC0101441-high-expression ECSCs (ECSCs-H) as extracellular vesicles (EVs)-generating cells and TC0101441-low-expression ECSCs (ECSCs-L) as recipient cells, we observed that the PKH67-labeled ECSCs-H-derived EVs were effectively internalized by ECSCs-L. ECSCs-H-derived EVs shuttling TC0101441 were transferred to ECSCs-L, modulating their migratory/invasive abilities partially by regulating certain metastasis-related proteins, which eventually facilitated endometriosis migration/invasion. This study elucidates a potential crosstalk between ECSCs via EVs in endometriotic milieus, suggests a novel mechanism for endometriosis migration/invasion from the perspective of the "extracellular vesicular transfer of lncRNAs" and highlights the potential of circulating extracellular vesicular TC0101441 as a biomarker for endometriosis.

Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologic surgeries: A systematic review.

Natural orifice transluminal endoscopic surgery (NOTES) is a significant innovation in the field of minimally invasive surgery. Transvaginal NOTES has gained the most popularity than other transluminal natural orifices such as mouth, rectum, urinary tract or vagina. Since vNOTES is introduced, many surgeons have developed the technique in various gynecologic surgeries. The aim is to collect the growing evidences of vNOTES in gynecological surgeries and highlight vNOTES with an acceptable safety profile. In the present literature review, the search was carried out using the PubMed database with the following keywords: "natural orifice transluminal endoscopic surgery", "NOTES", "natural orifice" and "gynecologic surgery". The current status of vNOTES in gynecologic surgeries was investigated. A total of 33 studies with 628 cases were included in the review. Our outcomes showed that vNOTES had been performed successfully in a series of surgical procedures including salpingectomy, ovarian cystectomy, myomectomy, hysterectomy, lymphadenectomy and sacrocolpopexy. Advances in technology have improved the feasibility of vNOTES as a treatment option for gynecologic surgeries. When the technical limitations are overcome, wide application of vNOTES is expected to increase. Further prospective and comparative studies are needed to clarify the application of the techniques in gynecologic surgeries.

Long noncoding RNA TC0101441 induces epithelial-mesenchymal transition in epithelial ovarian cancer metastasis by downregulating KiSS1.

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

Analysis of the reproductive outcomes and the size of the unicornuate uterus measured by magnetic resonance imaging and their relationship.

PURPOSE: To evaluate the relationship between the uterine size measured by pelvic magnetic resonance and reproductive outcome in women with a unicornuate uterus. METHODS: This was a retrospective study including 140 patients affiliated with unicornuate uterus diagnosed by the pelvic MR prior to their first pregnancy in the Obstetrics and Gynecology Hospital of Fudan University from April 2010 to December 2017. All the length of the unicornuate uterus were re-measured and recorded by skilled radiologists during the study period. We divided all the 140 participants with complete pelvic MR imaging into four groups by the best reproductive outcomes, which refers to Group 1 (primary infertility, n = 21), Group 2 ( < 24 weeks' gestation, n = 34), Group 3 (preterm delivery, 24-35 weeks' gestation, n = 13), Group 4 ( ≥ 35 weeks' gestation, n = 72), followed them up and then analyzed the data. RESULTS: Measurements of 140 patients with hemi-uteri were retrieved for analysis. The mean length of the uterine was 4.90  ± 0.56 cm. There were no significant differences in the uterine cavity length, cervical length, endometrial thickness and uterine wall thickness between the four groups while the uterine length (P = 0.001) was statistically significant. Women with uterine lengths ≥  4.5 cm were more likely to experience full-term delivery compared with the other group (P = 0.001). Ordinal multiple logistic regression analysis showed that the uterine length [OR = 9.03 (95% CI: 2.90-28.13)] and uterine cavity length [OR = 0.32 (95% CI: 0.06-2.04)] were independent protective factors for better obstetric outcomes CONCLUSION: The uterine length is a reliable prognostic factor for the gestational week of delivery and an appropriate antenatal surveillance factor of women with unicornuate uterus.

The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis.

OBJECTIVE: The transfer of long noncoding RNAs (lncRNAs) via exosomes to modulate recipient cells represents an important mechanism for disease progression. Antisense hypoxia-inducible factor (aHIF) is a well-known angiogenesis-related lncRNA. Here, we aimed to investigate the clinical implications of aHIF and exosomal aHIF in endometriosis and the involvement of exosome-shuttled aHIF in endometriosis angiogenesis. STUDY DESIGN: The distribution and expression of aHIF in ectopic, eutopic, and normal endometria was evaluated. Serum exosomal aHIF levels in patients with endometriosis were tested. The correlation between serum exosomal aHIF and aHIF expression in ectopic endometria was analyzed. Endometriotic cyst stromal cells (ECSCs)-derived exosomes were characterized. The internalization of exosomes by human umbilical vein endothelial cells (HUVECs) was observed. A series of in vitro assays were conducted to investigate the roles and mechanisms of exosomal aHIF in endometriosis angiogenesis. RESULTS: Clinically, aHIF was highly expressed in ectopic endometria and serum exosomes in patients with endometriosis. Serum exosomal aHIF was significantly correlated to aHIF expression in matched ectopic endometria. In vitro, PKH67-labeled exosomes derived from aHIF high expression ECSCs were effectively internalized by recipient HUVECs. Notably, exosome-shuttled aHIF was transferred from ECSCs to HUVECs, which in turn elicited proangiogenic behavior in HUVECs by activating vascular endothelial growth factor (VEGF)-A, VEGF-D, and basic fibroblast growth factor, thereby facilitating endometriosis angiogenesis. CONCLUSION: Our study illustrates a potential cell-cell communication between ECSCs and HUVECs in an ectopic environment, provides a novel mechanistic model explaining how ECSCs induce angiogenesis from the perspective of the "exosomal transfer of aHIF," and highlights the clinical value of circulating exosomal aHIF in endometriosis.

Natural antisense transcript of hypoxia-inducible factor 1 regulates hypoxic cell apoptosis in epithelial ovarian cancer.

PURPOSE: Hypoxia is a key stress that triggers apoptosis in various tumors, including epithelial ovarian cancer (EOC). Previous researches identified a hypoxia-upregulated lncRNA named "a natural antisense transcript of hypoxia-inducible factor 1 (aHIF)" in some tumors. However, the contribution of aHIF to EOC remains unclear. Here, we aimed to investigate the expression, function, and underlying mechanisms of aHIF in EOC progression under hypoxia. MATERIALS AND METHODS: Expression levels of aHIF in EOC tissues were tested. In vitro and in vivo assays were conducted to explore the function and mechanism of aHIF in hypoxia-induced EOC progression. RESULTS: aHIF levels were increased in EOC tissues and were upregulated by hypoxia in EOC cells. Functional data revealed that aHIF knockdown accelerated cell apoptosis under hypoxia and inhibited EOC tumorigenesis and tumor growth in vivo. Additionally, aHIF overexpression inhibited cell apoptosis and enhanced cell proliferation under hypoxia in EOC. Mechanistically, the dysregulation of certain key mitochondrial apoptosis pathway-related genes, including Bcl-2, Bax, Caspase-7, and Caspase-9, may partially explain aHIF-regulated EOC apoptosis and growth under hypoxia. CONCLUSION: These data provide the first convincing evidence that aHIF may inhibit EOC apoptosis and thereby promote tumor growth through activation of the mitochondrial apoptosis pathway under hypoxia. Our findings help clarify the role of lncRNA in hypoxia-induced EOC progression.

Exosomal Metastasis­Associated Lung Adenocarcinoma Transcript 1 Promotes Angiogenesis and Predicts Poor Prognosis in Epithelial Ovarian Cancer.

Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.

The role of oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy.

BACKGROUND AND OBJECTIVES: This study is aimed to investigate the possibility of preoperative oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy. MATERIALS AND METHODS: In this retrospective nonrandomized study, of the 30 patients with gynecological malignancies who had indications for laparoscopic para-aortic lymphadenectomy up to renal vessels, 15 were administered preoperative oral oil (oil a administration) (control group) at our hospital between September 2017 and June 2018. The chylous tube displaying rates, incidences of chylous leakage, and other perioperative data of the two groups were compared. RESULTS: Successful display of chylous tubes was observed in 93.3% (14/15) patients in the oil administration group. The chylous leakage was zero in the oil administration group, and 33.3% (5/15) in the control group. The postoperative drainage duration (4.1 ± 1.0 days vs 7.6 ± 1.4 days, P = 0.000), somatostatin application time (0 day vs 5.9 ± 0.8 days), and postoperative hospital stay (6.0 ± 2.3 days vs 9.1 ± 2.1 days, P = 0.001) were significantly shorter in the oil administration group. The total cost is lower in the oil administration group (4972.52 ± 80.54 dollars vs 6260.80 ± 484.47 dollars, P = 0.000). CONCLUSIONS: Preoperative oil administration is a feasible and effective method to display the chylous tubes and to prevent the chylous leakage in para-aortic lymphadenectomy.