Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

919 granules improve postpartum depression through the regulation of abnormal peripheral blood IL-1ß.

Postpartum depression (PPD) has a significant impact on the physical and mental health of mothers, potentially leading to symptoms such as low mood, fatigue, and decreased appetite. It may also affect the healthy growth of the infant. The onset of PPD is closely related to abnormalities in inflammation and the immune system. PPD patients exhibit abnormalities in the proportion of peripheral blood immune cells, along with an increase in pro-inflammatory cytokines. Excessive pro-inflammatory cytokines in peripheral blood can disrupt the blood-brain barrier (BBB) by activating astrocytes and reducing transendothelial electrical resistance (TEER), allowing peripheral immune cells or cytokines to enter the brain and trigger inflammation, ultimately leading to the onset of depression. In addition, PPD lacks safe and effective treatment medications. In this study, we collected peripheral blood from both healthy postpartum women and those with PPD, conducted single cell RNA sequencing (scRNA-seq), and used an in-house analytical tool scSTAR to reveal that PPD patients exhibit elevated proportions of peripheral blood cDC2 and Proliferation B cells, which are significantly correlated with IL-1ß. Additionally, animal experiments were designed to validate that 919 granules can improve PPD by modulating the levels of peripheral blood IL-1ß, providing a potential therapeutic mechanism for PPD treatment.

Submersed macrophytes Vallisneria natans and Vallisneria spinulosa improve water quality and affect microbial communities in sediment and water columns.

Healthy aquatic ecosystems are essential for human beings. However, anthropogenic activities severely worsen water quality. In this study, using assembling mesocosms, we developed an efficient and easy-to-handle method to monitor the water quality by measuring the electrical conductivity (EC) of water. Our data demonstrate that the growth of two submersed macrophytes, Vallisnerianatans and Vallisneria spinulosa, improves water quality by decreasing EC. Furthermore, using high-throughput DNA sequencing, we analyzed the microbial community abundance and structure in sediment and water columns with or without plant growth. We generated 33,775 amplicon sequence variants from 69 samples of four sediment groups (BkM, CtM, VnR, and VsR) and three water column sample groups (CtW, VnW, and VsW). The results show that the relative abundance of bacteria was higher in the sediment than in the water column. Moreover, the diversity and composition of microbiomes were altered by Vallisneria spp. growth, and the α-diversity of the microbial communities decreased due to submersed macrophytes in both the sediment and water columns. The ß-diversity of the microbial communities also varied significantly with or without Vallisneria spp. growth for both the sediment and water columns.

Sleep deprivation during pregnancy leads to poor fetal outcomes in Sprague-Dawley rats.

Sleep deprivation is a common problem during pregnancy, but its impact on the fetus remains unclear. We aimed to investigate the effect of sleep deprivation during pregnancy on fetal outcomes and its mechanism in Sprague-Dawley rats. Sleep deprivation was performed from gestational day(GD) 1-19 using a multiplatform method for 18 h/day. Rats were sacrificed on GD20, and their blood and placentas were collected. Fetal and placental parameters were ascertained. Melatonin, adrenocorticotropic hormone (ACTH) and corticosterone were also measured in serum. The levels of arylalkylamine N-acetyltransferase (AANAT) and two melatonin receptors MT1 and MT2, in placental tissues were detected by western blotting. The inflammatory status and oxidative stress in serum and placentas were investigated. Miscarriage and intrauterine growth restriction were observed in the sleep deprivation group. Sleep deprivation resulted in an increased fetal absorption rate, while fetal weight, crown-rump length and placental weight were reduced. Placental histopathology showed that the labyrinth ratio in the sleep deprivation group was significantly reduced, with hypoplastic villi and obviously decreased blood vessels. Sleep deprivation decreased melatonin in serum and the expression of AANAT, MT1 and MT2 in placental tissues, elevated the oxidative stress products 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde(MDA) in serum and 4-hydroxynonenal (4HNE) in the placenta, and decreased the antioxidants superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in serum. Serum proinflammatory cytokines including interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), necrotizing factor-alpha (TNF-α), and interleukin-8(IL-8), were all elevated by sleep deprivation, and the inflammatory regulatory factor nuclear factor-κB p65 (NF-κB p65) in the placenta was enhanced when examined by immunohistochemistry. Corticosterone levels were comparable between the two groups, although ACTH levels were elevated significantly in the sleep deprivation group. Our study revealed that sleep deprivation during pregnancy can adversely impact fetal outcomes. Melatonin may play an important role in this pathology through the oxido-inflammatory process.

The Extracellular Vesicle-Macrophage Regulatory Axis: A Novel Pathogenesis for Endometriosis.

Endometriosis (EMs) is a common disease among women whose pathogenesis is still unclear, although there are various hypotheses. Recent studies have considered macrophages the key part of the immune system in developing EMs, inducing inflammation, the growth and invasion of the ectopic endometrium, and angiogenesis. Extracellular vesicles (EVs) as novel intercellular vesicle traffic, can be secreted by many kinds of cells, including macrophages. By carrying long non-coding RNA (lncRNA), microRNA (miRNA), or other molecules, EVs can regulate the biological functions of macrophages in an autocrine and paracrine manner, including ectopic lesion growth, immune dysfunction, angiogenesis, and can further accelerate the progression of EMs. In this review, the interactions between macrophages and EVs for the pathogenesis of EMs are summarized. Notably, the regulatory pathways and molecular mechanisms of EVs secreted by macrophages during EMs are reviewed.

ITCH-Mediated Ubiquitylation of ITGB3 Promotes Cell Proliferation and Invasion of Ectopic Endometrial Stromal Cells in Ovarian Endometriosis.

Post-translational modification of proteins is involved in the occurrence of endometriosis (EM); however, the role of ubiquitination modification in EM remains unclear. Integrin ß3 (ITGB3) is one of the ß-subunits of integrins, which plays a key role in tumor progression. In this study, we investigated the roles of ITGB3 and ITCH, one of the ubiquitin E3 ligases, in ectopic endometrial stromal cells (ESCs) and EM. Primary ectopic ESCs and normal ESCs were isolated and purified. Western blot was used to detect the expression of ITGB3 and ITCH in ESCs. The interaction between ITGB3 and ITCH in ESCs was investigated by the co-immunoprecipitation and ubiquitylation analysis. With or without the overexpression of ITCH and/or ITGB3, the proliferation and invasion of ectopic ESCs were detected by the CCK8 assay and transwell migration assay, respectively. We found that ITGB3 is upregulated in ectopic ESCs from patients with EM. ITCH interacts with ITGB3 by co-immunoprecipitation, and ITCH-overexpressing significantly increased the ubiquitination of ITGB3. The data of the CCK8 assays showed that ITGB3 overexpression significantly promoted cell proliferation of ectopic ESCs at 12, 24, 48, and 72 h. The transwell migration assays showed that ITGB3 overexpression significantly enhanced the invasive ability. However, ITCH had the opposite effects in both assays. Our findings indicate that ITCH-mediated ubiquitylation of ITGB3 regulates the proliferation and invasion ability of ectopic ESCs in EM.

The role of long noncoding RNA H19 in gynecological pathologies: Insights into gene regulation and immune modulation (Review).

Long non­coding RNAs (lncRNAs) represent a class of versatile molecules that exhibit the potential to regulate gene expression at various levels, namely transcriptional, post­transcriptional and epigenetic, thereby influencing critical cellular processes such as proliferation, apoptosis, invasion and drug resistance. The lncRNA H19, among the earliest identified within this category, has emerged as a significant participant in the pathogenesis of a multitude of both malignant and benign gynecological diseases. An escalating body of evidence indicates a functionally pertinent network of lncRNA H19 coexpression linked with the extracellular matrix architecture and immune microenvironment during cancer progression. This association may provide insightful leads for the selection of innovative diagnostic biomarkers and assist in the delineation of potent pharmaceutical targets for gynecological oncology. The present comprehensive review presented a synthesis of the expression profiles and multifaceted implications of lncRNA H19 across a spectrum of gynecological pathologies.

LncRNA-LA16c-313D11.11,A Signature to Predict Endometrial Carcinoma Patients with a Better Survival.

The aim of this study was to develop and internally validate a nomogram of the probability EC patients surviving longer than 5 years. Quantitative real-time PCR (qRT-PCR) was implemented to analyze the expression of lncRNA-LA16c-313D11.11 in 60 EC tissues. The clinicopathological characteristics and follow-up data were retrospectively gathered and analyzed. To establish the prediction model, multivariate logistic regression analysis was applied, and the discrimination, calibration, and clinical practicability of the prediction model were assessed with a concordance index (C-index), calibration chart, and decision curve analysis. Bootstrap validation was performed for internal validation. The prediction factors included the age of patients, myometrial invasion, lymphovascular space invasion, histological subtype, and the expression of lncRNA-LA16C-313D11.11. The model demonstrated good calibration and modest discrimination (C-index = 0.860, 95% confidence interval: 0.724-0.946). Moreover, the interval validation achieved a high C-index value of 0.778. This study revealed the predictive value of lncRNA-LA16C-313D11.11 and successfully developed a nomogram for predicting EC patients survival longer than 5 years, which may facilitate the institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions.

An IGF1-expressing endometrial stromal cell population is associated with human decidualization.

BACKGROUND: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. RESULTS: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. CONCLUSIONS: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Hydrological isolation affected the chemo-diversity of dissolved organic matter in a large river-connected lake (Poyang Lake, China).

The transportation processes during aquatic systems regulate the ultimate chemistry of dissolved organic matter (DOM), and in recent years, climate changes and human activities have altered the hydrological patterns of many rivers and lakes, which generated some severe issues, such as hydrological isolation. However, how hydrological isolation affects variations of DOM chemistry in large lake systems is still poorly understood. Here, optical properties and molecular compositions of DOM samples derived from a large river-connected lake (Poyang Lake, China) and its nearby seasonal sub-lakes (formed by hydrological isolation) were characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS) and ultraviolet-visible (UV-Vis) spectroscopy. The results revealed more abundance of organic matter in sub-lakes than that in the main lake according to high dissolved organic carbon (DOC) concentrations and absorption coefficients (a254 and a280). Large proportions of CHOS formulas were identified by FT ICR MS in sub-lakes DOM, which were produced through Kraft reactions (sulfide/bisulfide + lignin CHO → CHOS) in the interface of sediment/water, and greatly contributed to aliphatic compounds. In addition, obvious variations of compounds (such as polyphenols, highly unsaturated and aliphatic compounds) and lability of DOM were observed between sub-lakes and main lakes, which were mainly caused by the different degradation pathways of DOM (photodegradation in sub-lakes while biodegradation in the main lake). Our results demonstrated that hydrological isolation has significant impacts on DOM chemistry, and provides an improved understanding of the DOM biogeochemistry process in Poyang Lake and supports the management of the large lake systems.

Estrogen Regulates the Expression and Function of lncRNA-H19 in Ectopic Endometrium.

Background: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of endometriosis and can be regulated by estrogen. This study aimed to investigate the role of estrogen in regulating the expression and function of lncRNA-H19 in endometriosis. Methods: Endometrial stromal cells (ESCs) were isolated from ectopic, eutopic endometrium with endometriosis and control endometrium without endometriosis, and lncRNA-H19 expression was detected using real-time polymerase chain reaction (RT-PCR). Ectopic endometrial stromal cells (ecESCs) were treated with 17ß-estradiol at 10-8mol/L for 0, 12, 24 and 48 hours, and lncRNA-H19 expressions of cells were evaluated using RT-PCR. After ecESCs were treated with 17ß-estradiol for 48 hours, lncRNA-H19 expression was knocked down and cell proliferative and invasive abilities were compared. Results: The expression of lncRNA-H19 in ecESCs was significantly higher than that in eutopic endometrial stromal cells (euESCs) and control ESCs. After treated with 17ß-estradiol, ecESCshadupregulatedlncRNA-H19 expression with time-dependent manner. Cell proliferation and invasion increased when estrogen upregulated lncRNA-H19 expression in ecESCs, however, cell proliferation restored and cell invasion did not change when lncRNA-H19 was knocked down in ecESCs. Conclusion: The expression and function of lncRNA-H19 was regulated by estrogen in ecESCs, which probably contributed to the pathogenesis of endometriosis.

Differential Growth Responses of Alternanthera philoxeroides as Affected by Submergence Depths.

Global climate change has resulted in an increase in intensity and frequency of flooding, plants living in lowlands, and shore areas have to confront submergence caused by flooding, submergence-tolerant plants usually respond by adopting either escape or quiescence strategies. While certain plants exhibit a changeover from escape strategy upon partial submergence to quiescence strategy under complete shallow submergence, it remains unknown whether plants completely submerged at different water depths would adjust their strategies to cope with the change in submergence depth. Alternanthera philoxeroides is an ideal species to explore this adjustment as it is widely distributed in flood-disturbed habitats and exhibits an escape strategy when completely submerged in shallow waters. We investigated the responses of A. philoxeroides in terms of morphology, anatomy, and non-structural carbohydrate metabolism by conducting experiments using a series of submergence depths (0, 2, 5, and 9 m). During the submergence treatment, environmental factors such as light, dissolved oxygen, and temperature for submerged plants were kept constant. The results showed that A. philoxeroides plants submerged at depth of 2 m presented an escape strategy via fast stem elongation, extensive pith cavity development, and small biomass loss. However, the retarded stem elongation, reduced pith cavity transverse area, and increased biomass loss along the water depth gradient indicated that A. philoxeroides altered its growth response as water depth increased from 2 to 9 m. It is found that the changeover of response strategies occurred at higher submergence depths (5-9 m). Based on the results of our experiments, we demonstrated that water depth played an important role in driving the change in strategy. The water-depth-dependent growth performance of A. philoxeroides would benefit the species in habit exploration and exploitation. Further studies should focus on the performances of plants when submerged at varied water depths with different light climates and dissolved oxygen content, and how water depths drive the response behaviors of the submerged plants.

IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra-/- (knockout of Il27ra) female mice. Moreover, knockout of Il27ra did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3. In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in Il27ra-/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.

Knockdown of lncRNA H19 suppresses endometriosis in vivo.

The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.

A novel prognostic nomogram utilizing the 2018 FIGO staging system for cervical cancer: A large multicenter study.

OBJECTIVE: To evaluate the prognostic performance of the revised 2018 FIGO staging system for cervical cancer. METHODS: This retrospective multicenter study enrolled cervical cancer patients with 2009 FIGO Stage IA1-IIA2 who underwent surgeries between January 2006 and December 2017 in four tertiary hospitals. Patients were restaged according to the 2018 FIGO staging system by reviewing their medical data. RESULTS: Of 3238 cervical cancer patients included, 1841 (56.9%) patients were restaged: 641 (34.9%) due to tumor size, 544 (29.5%) due to lymph node metastasis, 614 (33.4%) due to the inconsistency between pre- and postoperative assessments, and 42 due to the cancellation of invasion width in Stage IA. After restaging, a clear tendency of decreased recurrence-free survival (RFS) and overall survival (OS) with increasing stage was observed. Multivariate Cox analysis showed that 2018 FIGO stage, parametrial involvement, and histology were independent prognostic factors for both OS and RFS (P < 0.05). Based on these factors, we established predictive nomograms with c-indexes of 0.735 and 0.721, showing good predictive ability for cervical cancer. CONCLUSION: The revised 2018 FIGO staging system can better reflect the survival of cervical cancer patients. Based on it, we established a nomogram that can predict the prognosis of cervical cancer patients more precisely.

Knockdown of lncRNA H19 suppresses endometriosis in vivo

The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.

LncRNA H19 Overexpression in Endometriosis and its Utility as a Novel Biomarker for Predicting Recurrence.

Endometriosis has a high recurrence rate after treatment, and there are no effective recurrence predictors. LncRNA H19 has been found to be a predictor of the poor prognosis of multiple diseases. Here, we aimed to investigate the expression and clinical implications of lncRNAH19 in endometriosis and explore the clinical application value of lncRNAH19 for recurrence prediction. LncRNA H19 expression was evaluated in 104 ectopic and eutopic endometrial samples from patients with endometriosis and 50 control endometrial samples from patients without endometriosis. The association between lncRNA H19 expression and the clinical characteristics of endometriosis as well as its value as a potential predictor of recurrence were analyzed. LncRNA H19 expression in the ectopic and eutopic endometria of endometriosis patients was significantly higher than that in the normal endometrium. LncRNA H19 expression in the ectopic endometrium was associated with infertility, recurrence, bilateral ovarian lesions, an increased CA125 level, and revised American Fertility Society (rAFS) stage. Multivariate logistic regression analysis showed that age less than 40 years and lncRNA H19 overexpression in the ectopic endometrium were independent prognostic factors of endometriosis recurrence, and the receiver operating characteristic (ROC) curve showed that the sensitivity and specificity for predicting recurrence were 90.9% and 61.0%, respectively, when the lncRNA H19 expression level in the ectopic endometrium was higher than 0.0277. LncRNA H19 may be involved in the pathogenesis of endometriosis especially in the mechanism of recurrence and is a novel potential predictor of the recurrence of endometriosis.

Serum Circular FoxO3a Serves as a Novel Prognostic Biomarker in Squamous Cervical Cancer.

PURPOSE: Circular RNAs (circRNAs) are novel type of noncoding RNAs that play important roles and serve as noninvasive biomarkers in various cancers. In the present study, we focused on circFoxO3a and aimed to investigate its prognostic value as a novel serum biomarker for squamous cervical cancer (SCC). PATIENTS AND METHODS: Our study included 103 SCC patients from Obstetrics and Gynecology Hospital of Fudan University. Expression levels of circFoxO3a in the serum of patients with SCC were examined by reverse transcription­quantitative PCR (RT­qPCR). The correlation between serum circFoxO3a expression and clinicopathologic factors was analyzed. The Kaplan-Meier method and multivariate Cox regression analysis were applied to evaluate the independent prognostic factors for SCC. A prognostic predictive nomogram was constructed using R software. RESULTS: Levels of serum circFoxO3a were decreased in SCC patients compared with controls. Low expression of circFoxO3a was correlated with deeper stromal invasion and positive lymph node metastasis. Moreover, SCC patients with lower expression of serum circFoxO3a showed poorer prognosis, including both overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox analysis indicated low serum circFoxO3a levels to be an unfavorable prognostic factor for both OS and RFS, independent of positive lymph node metastasis. Notably, the predictive nomogram we established further confirmed that serum circFoxO3a is a useful tool for predicting survival in SCC. CONCLUSION: Altogether, our findings demonstrated that serum circFoxO3a could serve as a potential novel noninvasive predictive prognostic biomarker and therapeutic target for SCC.

Laparoscopic metroplasty for unicornuate uterus with a functional noncommunicating rudimentary horn.

OBJECTIVE: To evaluate the feasibility of laparoscopic metroplasty for the treatment of unicornuate uterus with a functional noncommunicating rudimentary horn. METHODS: Laparoscopic metroplasty was performed in one patient using traditional laparoscopy and four patients using robot-assisted laparoscopy from December 2013 to December 2017 at the Obstetrics and Gynecology Hospital of Fudan University. The records of the five patients were analyzed retrospectively. RESULTS: In all five patients the unicornuate uterus and functional noncommunicating rudimentary horn were unified into a single cavity without intraoperative or postoperative complications. Average operative time was 281 minutes (range, 204-330 minutes) and average blood loss was 180 mL (range, 100-300 mL). Postoperative hospital stay was 7 days (range, 5-11 days) and there was no re-admission. All patients were relieved of pain and had regular menstruation after surgery. Average follow-up time was 44 months (range, 22-70 months). One patient conceived by in vitro fertilization and embryo transfer 2 years after the operation and delivered twins by cesarean at 33 weeks. CONCLUSION: Laparoscopic metroplasty, with or without robotic assistance, is an acceptable alternative to resection for a noncommunicating rudimentary horn with a functional endometrium.

Circulating serum exosomal aHIF is a novel prognostic predictor for epithelial ovarian cancer.

PURPOSE: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software. RESULTS: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients. CONCLUSION: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.