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Objectives: This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received progestin therapy to spare fertility and, thus, improve the management of this patient group. Materials and methods: The PubMed, PMC, EMBASE, Web of Science, and Cochrane databases were searched for correlational studies published in English. Studies that evaluated the prognosis of patients with CAH or early-stage EC were pooled for a systematic review and meta-analysis. Results: In total, 31 eligible studies, including 8 prospective and 23 retrospective studies involving 1099 patients, were included in this analysis. The most commonly used progestin agents were medroxyprogesterone acetate (MPA, 47.0%) and megestrol acetate (MA, 25.5%). The total complete response (CR) rate was 75.8% (833/1099), and the median time to CR with first-line progestin therapy was 6 months. In total, 294 (26.8%) patients who achieved CR became pregnant spontaneously (28 cases) or through assisted reproductive technology (127 cases). During the median follow-up of 39 months, 245 (22.3%) women developed recurrence. Only one patient (0.09%) died of the disease. The meta-analysis showed that compared to a BMI<25 kg/m 2 and CAH, a body mass index (BMI) ≥25 kg/m 2 ( P =0.0004, odds ratios (OR), 0.4; 95% confidence interval, 0.3–0.6) and EC ( P =0.0000, OR, 0.3; 95% confidence interval, 0.2–0.6) were significantly associated with a higher likelihood of a CR. Patients with a BMI≥25 kg/m 2 ( P =0.0007, OR, 2.5; 95% confidence interval, 1.4–4.3), PCOS ( P =0.0006, OR, 3.4; 95% confidence interval, 1.5–7.9), and EC ( P =0.0344, OR, 2.8; 95% confidence interval, 1.4–5.3) had a significantly higher risk of recurrence. Conclusion: In general, patients with CAH or early-stage EC who were treated with progesterone therapy had a favorable prognosis. However, the recurrence risk was not insignificant. Weight control is crucial for improving the clinical management of this patient group.

Introduction and hypothesis This study aimed to compare the expression levels of extracellular matrix (ECM) and apoptosis proteins in the uterosacral ligament (USL) of patients with and without pelvic organ prolapse (POP). Methods The USL were obtained from patients with POP-Q ≥ III (n = 35) and without POP (n = 20). Immunohistochemistry (IHC) staining and RT-qPCR were conducted to assess the protein and mRNA levels, respectively. The levels of type I collagen (COLI), type III collagen (COLIII), matrix metalloproteinase (MMP)1, MMP2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, estrogen receptor (ER)α, ERβ and apoptosis-related gene B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax) in the USL were analyzed. Results The protein expression and mRNA levels of MMP2 and MMP9, mRNA levels of BAD and BAX, and protein expression of active cleaved-Caspase3 were significantly higher in the POP group. There were no evident differences in COLIII, MMP1 or ERβ expression at either the mRNA or protein level or in TIMP1, TIMP2 or Caspase3 by IHC between the two groups. However, obvious decreases in COLI and ERα were evident at both the mRNA and protein levels in the POP group, and the mRNA levels of TIMP1 and TIMP2 were also decreased compared to those of the control group. Conclusion ECM in the USL tissues of POP patients is remodeled compared with non-POP patients and is characterized by decreased synthesis and increased degradation of collagen; moreover, the levels of the main proteins involved in apoptosis are increased in POP tissue.

Introduction and hypothesis Pelvic organ prolapse (POP) is a common condition in older women that affects quality of life. Mechanical injury of the pelvic floor support system contributes to POP development. In our study, we aimed to examine the mechanical damage to human uterosacral ligament fibroblasts (hUSLFs) to preliminarily explore the mechanism of mechanical transduction in POP. Methods hUSLFs were derived from POP and non-POP patients. Mechanical stress was induced by the FX-5000 T-cell stress loading system. Student’s t-test was used for comparisons between different groups. Results We found that hUSLFs from POP patients were larger and longer than those from non-POP patients and exhibited cytoskeleton F-actin rearrangement. Collagen I and III expression levels were lower and matrix metalloproteinase 1 (MMP1) levels were higher in POP patients than in non-POP patients. Additionally, the apoptosis rate was significantly increased in POP patients compared to non-POP patients. After mechanical stretching, hUSLFs underwent a POP-like transformation. Cells became longer, and the cytoskeleton became thicker and rearranged. The extracellular matrix (ECM) was remodelled because of the upregulation of collagen I and III expression and downregulation of MMP1 expression. Mechanical stress also induced hUSLF apoptosis. Notably, we found that the p38 MAPK pathway was activated by mechanical stretching. Conclusions Mechanical stress induced morphological changes in ligament fibroblasts, leading to cytoskeleton and ECM remodelling and cell apoptosis. p38 MAPK might be involved in this process, providing novel insights into the mechanical biology of and possible therapies for this disease.