The value of surgery and the prognostic factors for patients with recurrent low-grade endometrial stromal sarcoma: a retrospective study of 38 patients.

OBJECTIVE: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. METHODS: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. RESULTS: After a median follow-up of 137.0 months (95% confidence interval=85.4-188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). CONCLUSIONS: The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis.

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.

Nodal staging score for adequacy of nodal staging in cervical cancer.

Background: Cervical cancer remains the fourth most common female malignancy with increasing newly cases around the world. It is of clinical value to precisely evaluate whether false negative nodal existed and develop a nodal staging model in cervical cancer. Materials and methods: Clinical data of cervical cancer patients was retrieved from the Surveillance, Epidemiology, and End Results database. Probability of missing nodal disease and nodal staging score (NSS) was computed to assess the nodal status of each individual.Prognostic value of NSS was assessed. Results: A total of 9056 individuals were in this study, with 5115 squamous cell carcinoma, 2791 adenocarcinoma, 512 adenosquamous carcinoma, and 638 other type individuals. A beta-binomial model was used to compute the probability of nodal disease in four histological types, respectively. False negative probability drastically decreased as more nodes examined. To reach 0.05 of false negative probability, it required at least 17 lymph nodes in squamous cell carcinoma patients,18 in adenocarcinoma, 12 in adenosquamous carcinoma patients and 14 in other types. To reach 0.95 of NSS, it took 10 lymph nodes in squamous cell carcinoma, 6 in adenocarcinoma, 10 in adenosquamous carcinoma and 7 in other types. Significant prognostic values of NSS quartiles subsets were found in all four histological sets. Conclusion: NSS tool enables adequate nodal staging of cervical cancer with significant prognostic value. Exact number of lymph nodes required for surgery in cervical cancer is specified based on histologic type.

Interaction between XRCC2 gene polymorphism and abdominal obesity on risk of endometrial carcinoma.

AIMS: The aim of this study was to investigate the impact of three single nucleotide polymorphisms (SNPs) within X-Ray Repair Cross Complementary Group 2 (XRCC2) gene and additional gene- abdominal obesity (AO) interaction with endometrial carcinoma (EC) risk. METHODS: Hardy-Weinberg equilibrium was tested for all participants by using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). The best SNP-SNP and gene-AO interaction combination among three SNPs within XRCC2 gene and AO was screened using generalized multifactor dimensionality reduction (GMDR). RESULTS: We employed the logistic regression analysis showed that rs718282-T allele is associated with increased EC risk, adjusted ORs (95%CI) were 1.67 (1.23-2.04). However, we did not find statistical association between rs3218536, and rs3218384 and EC susceptibility. GMDR analysis was used for SNP-SNP- and gene-abdominal obesity analysis. The cross-validation consistency and the testing accuracy for the interaction were calculated. The two-locus model between rs718282 and AO had a testing accuracy of 60.11%, which was significant at the p < .001 level, and this two- locus model was considered as the best model. It provided statistical evidence for rs718282 gene-AO interaction effects. The results indicated that AO influenced the EC risk depending on the rs718282 genotypes. Compared with non- AO subjects with rs718282-CC genotype, AO subjects with rs718282-CT or TT genotype had the highest EC risk, OR (95%CI) was 2.83 (1.67 - 4.02), after covariates adjustment. CONCLUSIONS: Both the rs718282- T allele, and its interaction with AO were associated with increased EC risk.

The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing.

Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.

Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are the "seeds" for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and treatment.

The feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 drives lipophagy to induce cisplatin resistance in epithelial ovarian cancer.

Platinum-taxane chemotherapy is the first-line standard-of-care treatment administered to patients with epithelial ovarian cancer (EOC), and faces the major challenge of cisplatin resistance. Aurora Kinase A (AURKA) is a serine/threonine kinase, acting as an oncogene by participating in microtubule formation and stabilization. In this study, we demonstrate that AURKA binds with DDX5 directly to form a transcriptional coactivator complex to induce the transcription and upregulation of an oncogenic long non-coding RNA, TMEM147-AS1, which sponges hsa-let-7b/7c-5p leading to the increasing expression of AURKA as a feedback loop. The feedback loop maintains EOC cisplatin resistance via activation of lipophagy. These findings underscore the feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 provides mechanistic insights into the combined use of TMEM147-AS1 siRNA and VX-680, which can help improve EOC cisplatin treatment. Our mathematical model shows that the feedback loop has the potential to act as a biological switch to maintain on- (activated) or off- (deactivated) status, implying the possible resistance of single use of VX-680 or TMEM147-AS1 siRNA. The combined use reduces both the protein level of AURKA using TMEM147-AS1 siRNA and its kinase activity using VX-680, showing more significant effect than the use of TMEM147-AS1 siRNA or VX-680 alone, which provides a potential strategy for EOC treatment.

Recent advances in tumor biomarker detection by lanthanide upconversion nanoparticles.

Early tumor diagnosis could reliably predict the behavior of tumors and significantly reduce their mortality. Due to the response to early cancerous changes at the molecular or cellular level, tumor biomarkers, including small molecules, proteins, nucleic acids, exosomes, and circulating tumor cells, have been employed as powerful tools for early cancer diagnosis. Therefore, exploring new approaches to detect tumor biomarkers has attracted a great deal of research interest. Lanthanide upconversion nanoparticles (UCNPs) provide numerous opportunities for bioanalytical applications. When excited by low-energy near-infrared light, UCNPs exhibit several unique properties, such as large anti-Stoke shifts, sharp emission lines, long luminescence lifetimes, resistance to photobleaching, and the absence of autofluorescence. Based on these excellent properties, UCNPs have demonstrated great sensitivity and selectivity in detecting tumor biomarkers. In this review, an overview of recent advances in tumor biomarker detection using UCNPs has been presented. The key aspects of this review include detection mechanisms, applications in vitro and in vivo, challenges, and perspectives of UCNP-based tumor biomarker detection.

Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis.

OBJECTIVE: To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC). METHODS: We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. RESULTS: Data from 18,375 patients in 15 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.32-0.59) and total recurrence (OR 0.72, 95%CI 0.58-0.89). ACR was also associated with significantly better overall survival (HR 0.66, 95%CI 0.57-0.76), progression-free survival (HR 0.56, 95%CI 0.39-0.81) and disease-free survival (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer.

Roles and mechanisms of CircRNAs in ovarian cancer.

Ovarian cancer (OC) is one of the female malignancies with nearly 45% 5-year survival rate. Circular RNAs (circRNAs), a kind of single-stranded non-coding RNAs, are generated from the back-splicing of cellular housekeeping noncoding RNAs and precursor messenger RNAs. Recent studies revealed that circRNAs have different biological function, including sponging miRNAs, encoding micropeptides, regulating stability of cytoplasmic mRNAs, affecting transcription and splicing, via interacting with DNA, RNA and proteins. Due to their stability, circRNAs have the potential of acting as biomarkers and treatment targets. In this review, we briefly illustrate the biogenesis mechanism and biological function of circRNAs in OC, and make a perspective of circRNAs drug targeting immune responses and signaling pathways in OC. This article can provide a systematic view into the current situation and future of circRNAs in OC.

Secular trend and risk factors of 30-day COPD-related readmission in Beijing, China.

Readmission due to chronic obstructive pulmonary disease (COPD) exacerbation contributes significantly to disease burden. Trend in readmission rate among COPD patients in China is not well characterized. We described the secular trend and identify risk factors of COPD-related 30-day readmission in Beijing during 2012-2017. In this retrospective cohort study, we used data from a citywide hospital discharge database in Beijing. We included patients ≥ 40 years with a primary diagnosis of COPD from 2012 to 2017. A total of 131 591 index admissions were identified. COPD-related 30-day readmission was defined as the initial admission with a primary diagnosis of COPD that occurs within 30 days from the discharge date of an index admission. Overall and annual 30-day readmission rates were calculated in the total population and subgroups defined by patient characteristics. We used multivariable logistic models to investigate risk factors for readmission and in-hospital mortality within 30 days. The overall 30-day COPD-related readmission rate was 15.8% (n = 20 808). The readmission rate increased from 11.5% in 2012 to 17.2% in 2017, with a multivariable-adjusted OR (95% CI) for annual change to be 1.08 (1.06-1.09) (P trend < 0.001). The upward trend in readmission rate levelled off at about 17% since 2014. The readmission rate of men was higher and increased faster than women. Comorbid osteoporosis, coronary heart disease, congestive heart failure, and cancer were associated with an increased risk of 30-day COPD-related readmission. The 30-day COPD-related readmission rate in Beijing showed an overall increasing trend from 2012 to 2017. Future efforts should be made to further improve care quality and reduce early readmissions of COPD patients.

Sperm-like nanocarriers for ultrafast delivery of antisense DNA.

Although various nanomaterials have been designed as intracellular delivery tools, the following aspects have become obstacles to limit their development, like a complex and time-consuming synthesis process, as well as relatively limited application areas (i.e. biosensing or cell imaging). Here, we developed a novel nano-delivery system called "nano-sperm" with low cytotoxicity and high biocompatibility. In this system, we used DNA oligonucleotides as a backbone to synthesize a nanostructure with silver nanoclusters in the head and functional fragments in the tail, which is shaped like a sperm, to achieve dual functions of ultrafast delivery and imaging/therapy. As a model, we analyzed the possibility of the "nano-sperm" carrying DNA with different structures for imaging or survivin-asDNA for tumor therapy. Therefore, this work reports a novel bifunctional high-speed delivery vehicle, which successfully fills the gap in the field of tumor therapy using DNA-templated nanoclusters as a delivery vehicle.

[Effectivity of Multiphase Fenton-like System of Iron Reduction Induced by Bisphenol A Authigenic Photoelectron].

In recent years, the Fenton-like (Fe2+-PMS/PS) advanced oxidation technology of persulfate activated by ferrous ions has been increasingly developed, but the difficulty of Fe3+ reduction, which stops the reaction, still restricts its large-scale application. In this study, it was found that when some organic compounds represented by bisphenol A (BPA) were mixed with Fe3+ and pristine TiO2, some surface structures could broaden the light response range of TiO2, capture visible light, and transfer the photoelectrons to Fe3+ through TiO2 for reduction, so as to achieve an infinite cycle of Fe3+/Fe2+. According to the above principle, a BPA-TiO2-Fe3+-PS composite system under visible light was constructed to degrade BPA, and its catalytic performance, catalytic mechanism, and influencing factors were discussed. The results showed that the system had outstanding catalytic performance, the degradation efficiency of BPA (50 mg·L-1) reached 93.1%, and the mineralization efficiency reached 70% within 60 min. At the same time, it verified that the system could reduce Fe3+ by the authigenic photoelectron of bisphenol A, and the steady-state concentration of Fe2+ obtained by 60 min reduction was 3.5 µmol·L-1. The main active oxidizing species in the system were sulfate radicals (SO4-[KG-*2/3]·) and hydroxyl radicals (·OH), of which the contribution rate of·OH was more than 60%. An appropriate increase in TiO2, Fe3+, and PS dosage and light intensity could improve the degradation effect. The system had the best treatment efficiency under weak acid conditions, and the degradation efficiency reached 96.5%. It also had a good effect under neutral conditions. CO32-, H2PO4-, and SO42- had a certain inhibitory effect on the system.

Adsorption of micropollutants from wastewater using iron and nitrogen co-doped biochar: Performance, kinetics and mechanism studies.

In this study, a novel iron and nitrogen co-doped biochar (Fe/N-biochar) was successfully prepared and employed as an efficient adsorbent for micropollutants. The maximum adsorption capacity of Fe/N-biochar for bisphenol A (BPA) was 54 mg/g, which is significantly better than that of commercial graphene (19 mg/g) and activated carbon (6 mg/g). Additionally, for eight other common micropollutants (e.g., phenol, acetaminophen, and sulfamethoxazole), Fe/N-biochar also exhibited highly enhanced adsorption performance. The results of adsorption kinetics and isotherms studies showed that the adsorption of micropollutants onto Fe/N-biochar is by monolayer coverage. Thermodynamic studies further suggested that the adsorption process is feasible, spontaneous, and chemical in nature. The adsorption mechanism was investigated by correlation analysis between the adsorption capacity and the physiochemical properties of Fe/N-biochar. The results demonstrated that the strengthening of π-π electron donor-acceptor interactions between the organics and the adsorbent caused by the co-doping of iron and nitrogen was the dominant driving force behind the efficient adsorption of micropollutants. Furthermore, graphitic N and Fe-Nx were identified as the major adsorption sites. Simple heat treatment could effectively restore the adsorption capacity of Fe/N-biochar that had reached adsorption equilibrium. In view of its simple preparation method, highly enhanced adsorption capacity, and excellent recyclability, the prepared Fe/N-biochar can be regarded as a promising candidate for wastewater treatment.

[Corrigendum] Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion.

Subsequently to the publication of the above paper, the authors have drawn to our attention that the middle panel in Fig. 3B, representing the migration of PIPKIγ­depleted cells (PIPKIγ­1), was inadvertently mixed up with the left panel of control cells (siRNA Ctrl). The results presented in Fig. 3D, however, were quantified based on the original images from three independent experiments, each containing five randomly picked micro-scopic fields. The authors were able to re­examine the original data files and retrieve the correct data panels. The revised version of Fig. 3, featuring the correct data for the 'PIPKIγ­1' panel in Fig. 3B, is shown below. Note that the error made inadvertently with the selection of the representative image for PIPKIγ­1 in Fig. 3B did not affect the overall conclusions reported for this experiment. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 38: 253­262, 2017; DOI: 10.3892/or.2017.5670].

A case report of primary multiple obturator nerve schwannomas.

Primary multiple obturator nerve schwannomas originate from Schwann cells and are extremely rare. Patients with schwannomas are asymptomatic and a retroperitoneal schwannoma is often misdiagnosed as an adnexal mass. In the present study, we describe a 58-year-old woman in whom a right adnexal mass accompanied by endometrial polyp was found incidentally through transvaginal ultrasound. The mass was diagnosed as multiple obturator nerve schwannomas after laparoscopy. Immunohistochemical assay confirmed the schwannomas to be positive for SOX10. To our knowledge, this is the first report to demonstrate a case of multiple schwannomas originating from the obturator nerve and treated by laparoscopic resection.

Therapeutic Effect of Human Amniotic Epithelial Cells in Rat Models of Intrauterine Adhesions.

As a refractory fibrosis disease, intrauterine adhesions (IUAs) is defined as fibrosis of the physiological endometrium. Although hysteroscopic adhesiolysis is widely recommended as an effective treatment, prognosis and recurrence remain poor in severe cases. Recently, stem cell therapy has been promoted as a promising treatment for IUAs. The ability of human amniotic epithelial cells (hAECs), emerging as a new candidate for stem cell therapy, to treat IUAs has not been demonstrated. To study the potential effects of hAECs on IUAs, we created an IUA rat model using mechanical injury and injected cultured primary hAECs into the rats' uteri. Next, we observed the morphological structure of endometrial thickness and glands using hematoxylin and eosin staining, and we detected extracellular-matrix collagen deposition using Masson staining. In addition, we performed immunohistochemical staining and reverse-transcription polymerase chain reaction (RT-PCR) to investigate potential fibrosis molecules and angiogenesis factors 7 d after hAECs transplantation. Finally, we detected estrogen receptor (ER) and growth factors via RT-PCR to verify the molecular mechanism underlying cell therapy. In the IUA rat models, endometrial thickness and endometrial glands proliferated and collagen deposition decreased significantly after hAEC transplantation. We found that during the recovery of injured endometrium, the crucial fibrosis marker transforming growth factor-ß (TGF-ß) was regulated and angiogenesis occurred in the endometrial tissue with the up-regulation of vascular endothelial growth factor. Furthermore, hAECs were shown to promote ER expression in the endometrium and regulate the inflammatory reaction in the uterine microenvironment. In conclusion, these results demonstrated that hAEC transplantation could inhibit the progression of fibrosis and promote proliferation and angiogenesis in IUA rat models. The current study suggests hAECs as a novel stem cell candidate in the treatment of severe IUA.

A Case Report Of Uterine Leiomyosarcoma.

BACKGROUND: Uterine leiomyoma is the most common benign tumor in women. Uterine sarcoma, though with very low incidence, has a high malignant degree and poor prognosis. It has difficulties in preoperative diagnosis, frozen pathological examination and postoperative treatment. CASE REPORT: A 49-year-old woman presented with menstrual disorder. Magnetic resonance imaging showed a huge uterine mass. The patient underwent laparoscopic hysterectomy and part of the uterine tissue looked like fish. Specimens were sent to frozen pathological examination for four times, but none of the results showed malignancy certainly. Considering all abnormalities, we removed the uterine through vagina completely rather than morcellation and did pelvic lymph node biopsy. Postoperative pathological examination revealed uterine leiomyosarcoma and one pelvic lymph node had metastasized. CONCLUSION: Uterine sarcoma is difficult to be diagnosed even frozen pathological examination has been performed. Unexpected uterine sarcoma should always be considered, and precautions should be taken if we find anything suspicious. Fortunately, the patient has avoided second operation.

Mechanisms of endometrial fibrosis and the potential application of stem cell therapy.

Fibrosis diseases result from excessive accumulation of extracellular matrix proteins which lead to normal tissue being replaced by fibrotic tissue or scar and eventually cause organ failure. Endometrial fibrosis is defined as the physiological endometrium becoming fibrosed, also known as intrauterine adhesions (IUA) or Asherman's syndrome, which progressively impairs endometrial function. On the basis of the fibrosis pathology, prevention of endometrial fibrosis is fundamental for IUA treatment, and elucidating the cellular and molecular mechanisms underlying endometrial fibrosis is imperative. Myofibroblasts play a crucial role in fibrosis formation. Thus, understanding the myofibroblasts' proliferation and the key signaling pathways is essential for implementing novel therapies of fibrosis diseases. Stem cell therapy is an emerging and potentially powerful therapeutic modality for refractory severe IUA patients in recent years. In this review, we discuss the role of myofibroblasts, summarize the key cellular and molecular mechanisms participating in the endometrial fibrosis process, and attempt to explain the anti-fibrosis mechanism under stem cell therapy.