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Introduction: Cervical insufficiency is an increased risk of midterm miscarriage and early preterm birth which increase the risk of fetal loss. This study aimed to construct a nomogram for patients with cervical insufficiency after cervical cerclage, which may assist clinicians to have individualized treatment for patients with cervical insufficiency. Methods: A study was done retrospectively from January 2013 through July 2022 in our hospital. The primary outcomes were delivered at more than 28, 30, 32, or 34 gestational weeks. Kaplan-Meier curves were applied to analyze 17 variables. All patients were randomly split (147:64) into development and validation cohorts. Based on the multivariate Cox regression analysis, a nomogram was constructed through the 'rms' package in R. Results: A total of 211 patients with cervical insufficiency were enrolled: 121 had history-indicated cerclage; 58 had ultrasound-indicated cerclage and 32 had emergency cerclage. Times of gestations, times of miscarriages, IVF, abdominal pain, diagnostic classification, preoperative and postoperative management were demonstrated to impact overall extended days when delivering at more than 28 gestational weeks was set as the primary outcome. Except for preoperative and postoperative management, the above other five variables impacted the primary outcomes of delivering at more than 30, 32, or 34 gestational weeks. Postoperative tocolytics had an impact on the prognosis of patients who delivered at more than 30 gestational weeks. In development cohort data, a nomogram was established to predict overall extended days of patients with cervical cerclage. In present study, C-index was 0.662 in the development cohort and 0.687 in the validation cohort respectively, suggesting that the model presented some satisfied prediction. Moreover, the clinical decision curves for patients with delivering at more than 28, 30, 32 or 34 weeks set as primary outcomes also displayed that this nomogram demonstrated good clinical predictive usefulness. Conclusions: The nomogram developed in this study may be a valuable tool assisting clinicians to evaluate outcomes of patients with cervical insufficiency after cervical cerclage, which helps them develop individualized management for the patients.

Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism involved in exosomal microRNA-320a (miR-320a) and Sirtuin 4 (SIRT4) was investigated in POI mouse ovaries oocytes and human granulosa cells (hGCs) by fluorescence-activated cell sorting (FACS), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence experiments. hAMSC-Exos improved proliferation, inhibited apoptosis, and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries. hAMSC-Exos elevated ovarian function and prohibited SIRT4 expression in oogenesis. The therapeutic effects were attenuated when miR-320a was knocked down. hAMSC-Exos decreased the ROS levels in POI hGCs and oocytes and improved ovarian weight and litter size, except for the Exosanti-miR-320a/POI group. Finally, hAMSC-Exos reduced the SIRT4 and ROS levels in POI ovaries and hGCs. The downstream protein expression (ANT2, AMP-dependent kinase [AMPK], and L-OPA1) was downregulated in the hGCs-SIRT4KD group but disappeared in the Exosanti-miR-320a/POI group. Our study is the first to illustrate the therapeutic potential of hAMSC-Exos in POI. Exosomal miR-320 plays a key role in the hAMSC-Exos-mediated effects on ovarian function via SIRT4 signaling.