Sandplay therapy could be a method to decrease disease activity and psychological stress in children with systemic lupus erythematosus.

OBJECTIVE: Although the prevalence rate of childhood-onset systemic lupus erythematosus (cSLE) is far lower than that of adults, cSLE has a high rate of organ involvement, rapid development and poor prognosis, which is more serious than that in adults. And studies have shown that a wide range of physiological, functional, nerve, and organ damage will have a great impact on the mental health of children. At present, there is no relevant psychological intervention research for cSLE in China. This paper aimed to explore the effect of Sandplay therapy on mental health and disease activity of children with cSLE. METHODS: Forty childrens with cSLE were randomly divided into control group (CG) and intervention group (IG); the CG were treated with glucocorticoid, immunosuppressant and other drugs, while the IG were treated with Sandplay therapy in addition to drug therapy, at the time of 0, 2, and 4 weeks after initial diagnosis, respectively. The questionnaire evaluation and related clinical indicators of the two groups were compared and analyzed (before psychotherapy intervention) at 0, 2, 4, and 12 weeks after initial diagnosis. RESULTS: There was no significant difference between the two groups in the evaluation of questionnaire and related clinical indicators at the time 0, 2 weeks after initial diagnosis respectively. At 12 weeks after the intervention, the score of Short version of the Children's Depression Inventory (CDI-S) in the IG was significantly lower than that in the CG, the score of The Screen for Child Anxiety Related Emotional Disorders (SCARED) scale in the IG was significantly lower than that in the CG, and the Pediatric Quality of Life Inventory (PedsQL 4.0) showed that the scores of social function, school performance, and emotional health of the IG were higher than those of the CG (p < 0.05), and the clinical indexes of the IG were better than those of the CG (p < 0.05). CONCLUSION: Sandplay therapy may help to slow down the occurrence and development of anxiety and depression and reduce disease activity in patients with cSLE.

Decision tree model predicts live birth after surgery for moderate-to-severe intrauterine adhesions.

BACKGROUND: After treatment of intrauterine adhesions, the rate of re-adhesion is high and the pregnancy outcome unpredictable and unsatisfactory. This study established and verified a decision tree predictive model of live birth in patients after surgery for moderate-to-severe intrauterine adhesions (IUAs). METHODS: A retrospective observational study initially comprised 394 patients with moderate-to-severe IUAs diagnosed via hysteroscopy. The patients underwent hysteroscopic adhesiolysis from January 2013 to January 2017, in a university-affiliated hospital. Follow-ups to determine the rate of live birth were conducted by telephone for at least the first postoperative year. A classification and regression tree algorithm was applied to establish a decision tree model of live birth after surgery. RESULTS: Within the final population of 374 patients, the total live birth rate after treatment was 29.7%. The accuracy of the model was 83.8%, and the area under the receiver operating characteristic curve (AUC) was 0.870 (95% CI 7.699-0.989). The root node variable was postoperative menstrual pattern. The predictive accuracy of the multivariate logistic regression model was 70.3%, and the AUC was 0.835 (95% CI 0.667-0.962). CONCLUSIONS: The decision tree predictive model is useful for predicting live birth after surgery for IUAs; postoperative menstrual pattern is a key factor in the model. This model will help clinicians make appropriate clinical decisions during patient consultations.

Study on CCDC69 interfering with the prognosis of patients with breast cancer through PPAR signal pathway.

Coiled-coil domain-containing protein 69 (CCDC69) is a novel gene and limited knowledge in known in breast cancer. In the present study, we aimed to explore the relationship between CCDC69 and breast cancer, demonstrate the clinicopathological significance and prognostic role of CCDC69 in breast cancer, and analyze the possible mechanism of CCDC69 affecting the prognosis of breast cancer. First, from GEO database, TIMER, GEPIA, and OncoLnc, we select CCDC69 as the potential gene which closely involved in breast cancer progression. Next, by real-time PCR detection, the expression of CCDC69 in breast cancer tissue was notably lower than that in normal breast tissues (p=0.0002). In addition, our immunohistochemistry (IHC) indicated that the positive expression rate of CCDC69 in the triple-negative breast cancer (TNBC) was lower than that in the non-TNBC (p=0.0362), and it was negatively correlated with the expression of Ki67 (p=0.001). Further enrichment analysis of CCDC69 and the similar genes performed on FunRich3.1.3 revealed that these genes were significantly associated with fat differentiation, and most of them were related to peroxisome proliferator-activated receptor (PPAR) signal pathway. Collectively, our findings suggest that CCDC69 is down regulated in breast cancer tissue especially in TNBC which has higher malignant grade and poorer clinical prognosis.

ß-Actin facilitates etoposide-induced p53 nuclear import.

As a tumor suppressor, p53 preserves genomic integrity in eukaryotes. However, limited evidence is available for the p53 shuttling between the cytoplasm and nucleus. Previous studies have shown that ß-actin polymerization negatively regulates p53 nuclear import through its interaction with p53. In this study, we found that DNA damage induces both ß-actin and p53 accumulation in the nucleus. ß-actin knockdown impaired the nuclear transport of p53. Additionally, ß-actin could interact with p53 which was enhanced in response to genotoxic stress. Furthermore, N terminal deletion mutants of p53 shows reduced levels of association with ß-actin. We further identified Ser15, Thr18 and Ser20 of p53 are critical to the ß-actin: p53 interaction, which upon mutation into alanine abrogates the binding. Taken together, this study reveals that ß-actin regulates the nuclear import of p53 through protein-protein interaction.

Overexpression of Lin28B Promoted the Proliferation of Adenomyotic Smooth Muscle Cells of the Junctional Zone via Regulating Let-7a.

The inner myometrium, also called the junctional zone (JZ), is believed to play a major role in the development of adenomyosis. Recently, we found that the lethal-7a (Let-7a) microRNA (miRNA) was clearly downregulated in the miRNA expression profiles of JZ smooth muscle cells (JZSMCs) of patients with adenomyosis. Lin28, including Lin28A and Lin28B, is responsible for the post-transcriptional downregulation of the Let-7 miRNA family. However, the expression pattern of Lin28 and the function of the Lin28/Let-7 axis in adenomyosis have not yet been identified. In this study, we aim to explore the potential roles of the Lin28/Let-7 axis in the development of adenomyosis. Immunohistochemistry, western blot, and reverse transcription polymerase chain reaction (RT-qPCR) were used to evaluate the Lin28 expression, respectively. The correlation between Let-7a, Lin28A, and Lin28B expression was further examined using Pearson's correlation analysis. RNA interference was used to inhibit Lin28B gene, and then Cell Counting Kit (CCK-8) assay was performed to detect the cell proliferation capacity. The results revealed that the expression levels of Lin28B were upregulated in the JZ of adenomyosis whatever about proteins or mRNA (P < 0.0001); furthermore, its mRNA expression level was negatively correlated with Let-7a (r = - 0.749, P < 0.0001). After inhibiting Lin28B gene, the proliferation capacity of JZSMCs in adenomyosis group decreased after 48 h (P < 0.05). These results indicated that Lin28B may be involved in the pathogenesis of adenomyosis by promoting the proliferation capacity of JZSMCs via regulating Let-7a.

Decreased Expression of Cannabinoid Receptors in the Eutopic and Ectopic Endometrium of Patients with Adenomyosis.

OBJECTIVE: Adenomyosis is a common gynecologic benign disease that may have a life-long negative impact on women. Previous studies have indicated that the endocannabinoid system may participate in the progress of endometriosis. Our research aims to analyze the expression patterns of the typical cannabinoid receptors (CB1 and CB2), the main constituents of the endocannabinoid system, in endometrial samples derived from patients diagnosed as adenomyosis or not. METHODS: Eutopic and corresponding ectopic endometrium from 45 premenopausal women diagnosed as adenomyosis and normal endometrium from 34 age-matched women lacking evidence of adenomyosis were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) to determine the CB1 and CB2 expression levels. RESULTS: In either the proliferative or the secretory phase, CB1 and CB2 protein and mRNA levels were both significantly lower in the eutopic and ectopic endometrium of adenomyosis when compared with normal endometrium. For women with adenomyosis, CB1 and CB2 protein and mRNA levels were much lower in the ectopic endometrium than the eutopic in both phases of the cycle. Both CB1 and CB2 protein and mRNA levels were increased during the secretory phase in normal endometrium, while CB1 lost its cyclic variation in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis. CONCLUSION: The decreased expression of CB1 and CB2 in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis suggests that cannabinoid receptors may participate in the pathogenesis of adenomyosis.

Decision Tree Analysis: A Retrospective Analysis of Postoperative Recurrence of Adhesions in Patients with Moderate-to-Severe Intrauterine.

OBJECTIVE: To establish and validate a decision tree model to predict the recurrence of intrauterine adhesions (IUAs) in patients after separation of moderate-to-severe IUAs. DESIGN: A retrospective study. SETTING: A tertiary hysteroscopic center at a teaching hospital. POPULATION: Patients were retrospectively selected who had undergone hysteroscopic adhesion separation surgery for treatment of moderate-to-severe IUAs. INTERVENTIONS: Hysteroscopic adhesion separation surgery and second-look hysteroscopy 3 months later. MEASUREMENTS AND MAIN RESULTS: Patients' demographics, clinical indicators, and hysteroscopy data were collected from the electronic database of the hospital. The patients were randomly apportioned to either a training or testing set (332 and 142 patients, respectively). A decision tree model of adhesion recurrence was established with a classification and regression tree algorithm and validated with reference to a multivariate logistic regression model. The decision tree model was constructed based on the training set. The classification node variables were the risk factors for recurrence of IUAs: American Fertility Society score (root node variable), isolation barrier, endometrial thickness, tubal opening, uterine volume, and menstrual volume. The accuracies of the decision tree model and multivariate logistic regression analysis model were 75.35% and 76.06%, respectively, and areas under the receiver operating characteristic curve were 0.763 (95% CI 0.681-0.846) and 0.785 (95% CI 0.702-0.868). CONCLUSIONS: The decision tree model can readily predict the recurrence of IUAs and provides a new theoretical basis upon which clinicians can make appropriate clinical decisions.

FAK regulates epithelial­mesenchymal transition in adenomyosis.

Epithelial­mesenchymal transition (EMT) has been associated with the pathogenesis of adenomyosis; focal adhesion kinase (FAK) serves an important role in the EMT process. The aim of the present study was to determine whether FAK regulates EMT in adenomyosis and to investigate the potential pathway in this process. The expression of FAK and EMT­associated molecules in adenomyosis and control cells were determined by immunohistochemical staining and immunofluorescence at the protein level, and at the mRNA level by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Small interfering RNAs were designed to knock down FAK expression. Subsequently, molecular expression was detected by immunofluorescence, RT­qPCR and western blotting; cell migration was investigated via Transwell assays. In addition, the expression levels of members of the phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway was also analyzed by RT­qPCR and western blotting to determine the association between these members and EMT in adenomyosis. The results of the present study revealed that FAK was upregulated and the expression levels of EMT­associated molecules were altered in adenomyosis. Silencing FAK expression inhibited adenomyosis cell migration in vitro and the expression of EMT­promoting molecules, suggesting that the FAK/PI3K/AKT signaling pathway may participate in the EMT of endometrial cells in adenomyosis. In conclusion, FAK may regulate EMT in adenomyosis, and this process may be associated with the PI3K/AKT signaling pathway.

The Investigation and Management of Adenomyosis in Women Who Wish to Improve or Preserve Fertility.

The management of adenomyosis remains a great challenge to practicing gynaecologists. Until recently, hysterectomy has been the only definitive treatment in women who have completed child bearing. A number of nonsurgical and minimally invasive, fertility-sparing surgical treatment options have recently been developed. This review focuses on three aspects of management, namely, (1) newly introduced nonsurgical treatments; (2) management strategies of reproductive failures associated with adenomyosis; and (3) surgical approaches to the management of cystic adenomyoma.

Expression Pattern of G-Protein-Coupled Estrogen Receptor in Myometrium of Uteri with and without Adenomyosis.

OBJECTIVE: To compare the expression of G-protein-coupled estrogen receptor (GPER) in the junctional zone and outer myometrium of the proliferative and secretory phases of women with and without adenomyosis. METHODS: A total of 76 women were included in this study, 42 with adenomyosis (proliferative phase, n = 23; secretory phases, n = 19) and 34 controls (proliferative phase, n = 16; secretory phases, n = 18). Protein and total RNA were extracted from the junctional zone (JZ) and outer myometrium (OM). GPER protein and mRNA expression levels were evaluated by the use of western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression of GPER protein and mRNA in women with adenomyosis was significantly higher than that of control subjects, both in the junctional zone and in the outer myometrium and both in the proliferative and in the secretory phases. CONCLUSION: The significant and consistent increase in GPER expression in adenomyosis compared with control subjects, regardless of whether it was in the proliferative or secretory phases and regardless of whether it was in the JZ or OM, suggests that GPER plays an important role in the pathogenesis of the adenomyosis.

Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

BACKGROUND AIMS: Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. METHODS: Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. RESULTS: Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. CONCLUSIONS: hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria.

17ß-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway.

Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. Recent models favor abnormal thickening of the junctional zone (JZ) may be the causative factor in the development of ADS. RhoA, a small guanosine triphosphatase which controls multiple cellular processes, is involved in the control of cell proliferation. Here we demonstrate that treatment of human uterine smooth muscle cells (SMCs) of the JZ with 17ß-estradiol (E2) increased expression of RhoA and its downstream effectors (-associated coiled coil containing protein kinase [ROCK] 1 and ROCK2). Compared with non-ADS cells, RhoA, ROCK1, and ROCK2 were overexpressed and hyperactivated in ADS cells. These effects were suppressed in the presence of ICI 182,780, supporting an estrogen receptor (ER)-dependent mechanism. Hyperactivation of ER-enhanced RhoA/ROCK signaling was associated with overproliferation in ADS human uterine SMCs of the JZ. Moreover, E2-induced overproliferation was accompanied by downregulation of cyclin-dependent kinases inhibitors (CKIs; p21(Waf1/Cip1) and p27(Kip1)) and upregulation of cyclin-dependent kinases (CDKs) and cyclins (cyclin D1, cyclin E1, CDK2, CDK4, and CDK6).

Actin polymerization negatively regulates p53 function by impairing its nuclear import in response to DNA damage.

Actin, one of the most evolutionarily conservative proteins in eukaryotes, is distributed both in the cytoplasm and the nucleus, and its dynamics plays important roles in numerous cellular processes. Previous evidence has shown that actin interacts with p53 and this interaction increases in the process of p53 responding to DNA damage, but the physiological significance of their interaction remains elusive. Here, we show that DNA damage induces both actin polymerization and p53 accumulation. To further understand the implication of actin polymerization in p53 function, cells were treated with actin aggregation agent. We find that the protein level of p53 decrease. The change in p53 is a consequence of the polymeric actin anchoring p53 in the cytoplasm, thus impairing p53 nuclear import. Analysis of phosphorylation and ubiquitination of p53 reveals that actin polymerization promotes the p53 phosphorylation at Ser315 and reduces the stabilization of p53 by recruiting Aurora kinase A. Taken together, our results suggest that the actin polymerization serves as a negative modulator leading to the impairment of nuclear import and destabilization of p53. On the basis of our results, we propose that actin polymerization might be a factor participating in the process of orchestrating p53 function in response to DNA damage.