Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women: a randomized, controlled trial.

Intrauterine adhesion is a major cause of female reproductive disorders. Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth, no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far. To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate, we conducted this randomized controlled clinical trial. Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter (control group) from February 2016 to January 2020. The per-protocol analysis included 140 participants: 72 in bone marrow stem cells-scaffold group and 68 in control group. The ongoing pregnancy occurred in 45/72 (62.5%) participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group (28/68, 41.2%) (RR=1.52, 95%CI 1.08-2.12, P=0.012). The situation was similar in live birth rate (bone marrow stem cells-scaffold group 56.9% (41/72) vs. control group 38.2% (26/68), RR=1.49, 95%CI 1.04-2.14, P=0.027). Compared with control group, participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis. The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed. In conclusion, transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates, and this therapy was relatively safe.

Construction of a transition-metal sulfide heterojunction photocatalyst driven by a built-in electric field for efficient hydrogen evolution under visible light.

Photocatalytic H2 evolution is of prime importance in the energy crisis and in lessening environmental pollution. Adopting a single semiconductor as a photocatalyst remains a formidable challenge. However, the construction of an S-scheme heterojunction is a promising method for efficient water splitting. In this work, CdS nanoparticles were loaded onto NiS nanosheets to form CdS/NiS nanocomposites using hollow Ni(OH)2 as a precursor. The differences in the Fermi energy levels between the two components of CdS and NiS resulted in the formation of a built-in electric field in the nanocomposite. Density functional theory (DFT) calculations reveal that the S-scheme charge transfer driven by the built-in electric field can accelerate the effective separation of photogenerated carriers, which is conducive to efficient photocatalytic hydrogen evolution. The hydrogen evolution rate of the optimized photocatalyst is 39.68 mmol·g-1 h-1, which is 6.69 times that of CdS under visible light. This work provides a novel strategy to construct effective photocatalysts to relieve the environmental and energy crisis.

High-performance, self-powered flexible MoS2 photodetectors with asymmetric van der Waals gaps.

With an urgent demand for low-energy-consumption and wearable devices, it is desirable to find an easy, effective, and low-cost method to fabricate self-powered flexible photodetectors with simple configurations and high-performance. Self-powered photodetectors are normally fabricated based on either two different materials or the same material in contact with two different metal electrodes. Here, a flexible MoS2 photodetector with the same Au electrodes was fabricated on a polyethylene terephthalate (PET) substrate which exhibits self-powered properties. To our knowledge, its configuration is the simplest, and the fabrication process is easy to implement. At a bias of 0 V, the photodetector exhibits a high responsivity of 431 mA W-1, a short response/recovery time of 40 ms/40 ms, and excellent flexibility. Compared with those at a bias of 2 V, a dark current is sufficiently suppressed, and the response/recovery speed is significantly improved. It is found that the driving force of the self-powered photodetector is provided by the asymmetric Schottky barriers originating from the spontaneous generation of two van der Waals gaps with different widths. The asymmetric barriers exist stably at the interfaces between the 2D material and Au electrodes as further observed for ReS2 or GaSe flakes, which show the generality of asymmetric Schottky barriers between the 2D material and Au electrodes. The discovery here thus gives a new way to generate asymmetric Schottky barriers and develop high-performance self-powered photodetectors.

Construction of a Glycolysis-related long noncoding RNA signature for predicting survival in endometrial cancer.

Background: long noncoding RNA (lncRNA) has been widely studied and understood in various cancer types. However, the expression profiles of glycolysis-related lncRNA in endometrial cancer (EC) have poorly been reported. Methods: In this study, we retrieved the "Glycolysis" gene list from Molecular Signatures Database (MSigDB) and screened prognostic glycolysis-related lncRNA using The Cancer Genome Atlas (TCGA) Uterine Corpus Endometrial Carcinoma (UCEC) RNA-seq dataset. Then, TCGA UCEC patients were randomly divided. Lasso algorithm and multivariate cox regression analyses were then performed to further select hub prognostic lncRNA and to develop a prognostic signature. The efficacy of the signature was also evaluated in the TCGA EC cohort. Moreover, we constructed a nomogram to predict EC patient outcomes. Results: Univariate cox analysis identified thirty-six glycolysis-related lncRNA correlated with EC patient prognosis. Among them, five lncRNA were further selected as hub lncRNA that mostly relate to EC patient outcomes, which are AL121906.2, BOLA3-AS1, LINC01833, AC016405.3, and RAB11B-AS1. A prognostic signature was then built based on the expression and coefficiency of five lncRNA. The efficacy of the signature was validated in part of and the entire TCGA EC cohort. In addition, the risk signature could precisely distinguish high- and low-risk EC patients and predict patient outcomes. The nomogram exhibited absolute concordance between the predictions and actual survival observations. Conclusions: The glycolysis-related lncRNA signature model and the nomogram may provide a new perspective for EC patients outcome prediction in clinical use.

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.

Collagen-binding basic fibroblast growth factor improves functional remodeling of scarred endometrium in uterine infertile women: a pilot study.

Intrauterine adhesion (IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2 (bFGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of bFGF 100 µg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients (2-4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved. Histological study showed blood vessel density increased obviously. Three patients (3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the bFGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.

Metastasis-associated protein 1, modulated by miR-30c, promotes endometrial cancer progression through AKT/mTOR/4E-BP1 pathway.

OBJECTIVE: Though metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with advanced clinicopathological characteristics and survival in related diseases, the association between MTA1 and endometrial cancer (EC) is little known and needs to be studied. METHODS: Western blot and immunohistochemistry were used to analyze protein expression level of cells and tissues, while real-time PCR was used for RNA detection. Bioinformatics tool analysis revealed the relationship between MTA1 and clinicopathological characteristics and survival. CCK-8 assay, colony-formation assay, cell scratch assay, and Transwell assay were performed to determine cell proliferation, migration and invasion abilities, respectively. RESULTS: The expression level of MTA1 was significantly higher in human EC tissues than in normal endometrium. MTA1 expression was correlated positively with lymph nodes metastasis and poor survival rate in EC. Experimentally overexpressed MTA1 could promote cell proliferation, migration and invasion abilities of EC cell lines Ishikawa, HEC-1B, and RL-952, while reduction of MTA1 inhibited these cell biological behaviors. Moreover, MTA1 could also reverse the negative effect of miR-30c, a direct modulator of MTA1, on EC cells. Our research also revealed that overexpression of MTA1 contributed to EC tumor growth, while knockdown of MTA1 resulted in tumor growth inhibition. Additionally, the phosphorylation levels of mTOR (S2448) and 4E-BP1 (T37/46) changed significantly along with AKT (T308) under regulation of MTA1, both in vivo and vitro. CONCLUSION: Our results showed that MTA1, as a downstream target of miR-30c, might promote EC progression via AKT/mTOR/4E-BP1 pathway, which indicated the potential therapy target of MTA1 in EC.

Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial.

BACKGROUND: Intrauterine adhesions (IUA) are the most common cause of uterine infertility and are caused by endometrium fibrotic regeneration following severe damage to the endometrium. Although current stem cell treatment options using different types of autologous stem cells have exhibited some beneficial outcomes in IUA patients, the reported drawbacks include variable therapeutic efficacies, invasiveness and treatment unavailability. Therefore, the development of new therapeutic stem cell treatments is critical to improving clinical outcomes. METHODS: Twenty-six patients who suffered from infertility caused by recurrent IUA were enrolled in this prospective, non-controlled, phase I clinical trial with a 30-month follow-up. During the procedure, 1 × 107 umbilical cord-derived mesenchymal stromal cells (UC-MSCs), loaded onto a collagen scaffold, were transplanted into the uterine cavity following an adhesion separation procedure. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and the biological molecules related to endometrial proliferation and differentiation were assessed both before and 3 months after cell therapy. RESULTS: No treatment-related serious adverse events were found. Three months after the operation, the average maximum endometrial thickness in patients increased, and the intrauterine adhesion score decreased compared to those before the treatment. A histological study showed the upregulation of ERα (estrogen receptor α), vimentin, Ki67 and vWF (von Willebrand factor) expression levels and the downregulation of ΔNP63 expression level, which indicates an improvement in endometrial proliferation, differentiation and neovascularization following treatment. DNA short tandem repeat (STR) analysis showed that the regenerated endometrium contained patient DNA only. By the end of the 30-month follow-up period, ten of the 26 patients had become pregnant, and eight of them had delivered live babies with no obvious birth defects and without placental complications, one patient in the third trimester of pregnancy, and one had a spontaneous abortion at 7 weeks. CONCLUSIONS: Transplanting clinical-grade UC-MSCs loaded onto a degradable collagen scaffold into the uterine cavity of patients with recurrent IUA following adhesiolysis surgery is a safety and effective therapeutic method. TRIAL REGISTRATION: Clinicaltrials.gov . NCT02313415 , Registered December 6, 2014.

Management and obstetric outcomes of 17 heterotopic interstitial pregnancies.

BACKGROUND: Heterotopic interstitial pregnancy is a rare variant of heterotopic pregnancies, and it poses challenges in treating the heterotopic pregnancy and preserving the intrauterine pregnancy. However, there is no clear consensus regarding the optimal management. The aim of this study was to investigate the pregnancy outcomes of women diagnosed with heterotopic interstitial pregnancy. METHODS: A total of 17 women diagnosed with heterotopic interstitial pregnancy between July 2010 and December 2015 were included. General characteristics of each patient, including age, gravidity and parity, history of pelvic inflammatory disease or surgery, and especially the corresponding therapeutic interventions, were retrospectively analyzed. Moreover, pregnancy outcomes were further followed by face-to-face interview. RESULTS: Of the 17 patients, 10 (58.5%) underwent surgical treatment (7 laparoscopic cornual resection, and 3 laparotomy); and 3 cases simultaneously terminated the intrauterine pregnancy by suction evacuation. Compared with laparotomy, laparoscopic cornual section showed shorter operative time (median 40 vs. 70 min), less blood loss (150 vs. 400 ml) and shorter hospital stay (2 vs. 4 days). In addition, 4 (23.5%) patients underwent selective embryo reduction under transvaginal ultrasound guidance. Expectant management was chosen in the remaining 3 patients. In the follow-up study, other than a case of missed miscarriage, the other 13 women who remained committed to their pregnancies all delivered healthy babies either by caesarean section or vaginal birth. No congenital anomalies were reported, and all the infants were in good growth and development. CONCLUSIONS: Laparoscopic cornual resection is a feasible approach with favorable surgical and long-term pregnancy outcomes. Additionally, medical or expectant management may be a viable treatment option for selected symptom-free patient. Although the survival of the intrauterine pregnancy could not always be assured, the prognosis for a woman with heterotopic interstitial pregnancy is generally good.

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome.

Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.

[Efficacy of conservative laparoscopic surgery combined with goserelin in treatment of 206 patients with severe ovarian endometriosis at short-term and long-term follow-up].

OBJECTIVE: To evaluate the short-term and long-term efficacy of conservative laparoscopic surgery combine with goserelin in treatment of severe ovarian endometriosis. METHODS: From January 2004 to December 2008, 206 patients with severe ovarian endometriosis underwent laparoscopy surgery in Nanjing Drum Tower Hospital, Affiliated Nanjing University Medical School were enrolled in this retrospective study. According to the revised classification American Fertility Society (r-AFS), 123 (123/206, 59.7%) cases were at stage III and 83 (83/206, 40.3%) patients were at stage IV. Among 138 cases presented pelvic pain. All the patients underwent laparoscopic cystectomy, of which 117 patients with childbearing preserving underwent hysteroscopy and hydrotubation examination, including 7 cases with bilateral salpingectomy, 2 cases with bilateral tubal obstruction and 108 cases with normal reproduction. After surgery, all cases were administered by goserelin treatment at dose of 3.6 mg per 28 days for 3 to 6 months. At 1 to 5 years following up, pelvic pain, pregnancy and recurrence were observed, those factors associated with pregnancy rate and endometriosis recurrence were analyzed. RESULTS: (1) Pelvic pain: complete remission rate of pelvic pain was 76.1% (105/138) at 1 to 5 years after surgery. (2) Pregnancy: total pregnancy rate was 70.4% (76/108), spontaneous pregnancy rate was 68.8% (66/96) and pregnant rate of in vitro fertilization and embryo transfer (IVF-ET) was 10/12. Pregnancy rate at 1 year was 57.3% (55/96) and accounting for 83.3% (55/66) in all pregnant women. Live birth rates of spontaneous pregnant and IVF-ET were 86.4% (57/66) and 9/10, respectively. (3) Recurrence: the total recurrence rate was 8.3% (17/206) at 1 to 5 years. The recurrence rates and the cumulative recurrence rates were 3.9% (8/206) and 3.9% (8/206) at the first year after operation, 2.0% (3/149) and 6.7% (10/149) at the second year, 1.0% (1/99) and 8.0% (8/99) at the third year, 10.9% (5/46) and 17.4% (8/46) at the fourth year, 0 and 2/18 at the fifth year, respectively. CONCLUSION: It was suggested that conservative laparoscopic surgery combined with goserelin in treatment of stage III or IV ovarian endometriosis could reduce the recurrence risk of severe ovarian endometriosis and improve the pregnant rate of endometriosis-associated infertility.