Comparing levonorgestrel intrauterine system versus hysteroscopic resection in patients with postmenstrual spotting related to a niche in the caesarean scar (MIHYS NICHE trial) : Protocol of a randomised controlled trial

Funding This work was supported by National Key Research and Development Programme (2018YFC1002102), Research Project of Shanghai Health and Fitness Commission (201940012,20184Y0344)),Shanghai Municipal Key Clinical Specialty (shslczdzk01802), Medical Engineering Cross Funds from Shanghai Jiao Tong University (YG2017QN38, ZH2018QNA36, YG2021ZD31), Medical innovation research project of the 2020 'Science and Technology Innovation Action Plan' of Shanghai Science and Technology Commission (20Y11907700), and Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center(SHDC22020216).Peer reviewedPublisher PD

The effect of a hysteroscopic niche resection compared with Levonorgestrel-releasing intrauterine device on postmenstrual spotting in patients with a symptomatic niche in the uterine cesarean scar: A prospective cohort study

Objective: To compare the effect of a hysteroscopic niche resection with a Levonorgestrel-releasing intrauterine device (LNG-IUD, 52 mg) on postmenstrual spotting duration in patients with a symptomatic niche in the uterine cesarean scar. Study design: This prospective cohort study was conducted at the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, China. Patients with postmenstrual spotting symptomatic niches were allocated to hysteroscopy group or LNG-IUD group based on the shared medical decision-making approach, and were followed up for 1 year after treatment. Main outcome measures: The primary outcome was reduced postmenstrual spotting days at 6th month after treatment. Secondary outcomes were effectiveness rate (proportion of patients with spotting days reduced by at least 50% from baseline), menstrual characteristics, menstruation satisfaction, direct medical costs, complications and side effects. Results: 78 out of the 82 eligible patients were included, 36 patients in both group finished 1-year follow-up. Reduced spotting days at the 6th month was 7 days in LNG-IUD group, significantly higher than 5 days in hysteroscopy group, P = 0.004; The effectiveness rate increased over time within 1 year after the insertion of LNG-IUD (63.89%, 83.33%, 88.89%, 88.89%, P for trend = 0.006), while no trend change was observed in hysteroscopy group (71.05%, 71.05%, 66.67%, 61.11%, P for trend = 0.77). The mean direct medical costs were 817[785,856] $in the hysteroscopy group and 243[239,255]$ in the LNG-IUD group (p＜0.001). 2 patients removed IUD and 2 patients reported weight gain of more than 5 kg and breast distended pain in LNG-IUD group; 2 patients got pregnant in hysteroscopy group. No serious complications were observed in both groups. Conclusions: LNG-IUD is more effective in the treatment of postmenstrual spotting from the 6th month onwards than a hysteroscopic niche resection in patients with a symptomatic niche at lower direct costs

Fabrication of an All-Solid-State Carbonate Ion-Selective Electrode with Carbon Film as Transducer and Its Preliminary Application in Deep-Sea Hydrothermal Field Exploration

Real-time measurements of carbonate ion concentrations in the ocean are critical to advancing marine environmental monitoring and research into deep-sea hydrothermal activity. Herein, we report the first example of deep-sea hydrothermal field exploration using a carbonate ion-selective electrode (ISE). The novel carbonate ISE was composed of a Ni wire as substrate, carbon film as transducers and carbonate-selective membrane layers. This paper describes the preparation process of the electrode and characterises its performance via scanning electron microscopy (SEM) and electrochemical analysis. The detection limit of the electrode for CO32− is 2.821 × 10−6 mol/L, the linear response range is 1.0 × 10−5–1.0 × 10−1 mol/L and the Nernst slope was −30.4 mV/decade. In April 2021, the carbonate ISE was mounted on multi-parameter sensors with pH and Eh (redox) electrodes for the search of hydrothermal activity at the Southwest Indian Ridge. The simultaneous potential anomalies appeared at this carbonate electrode with the pH and Eh electrodes when passing through the hydrothermal field. The study of the hydrothermal field was supported by the in situ camera video and the sulphide samples. Additionally, the carbonate electrode provides enhanced information of water chemistry for the study of the hydrothermal field

Fertility outcomes after hysteroscopic niche resection compared with expectant management in women with a niche in the uterine cesarean scar

Objective: To determine whether hysteroscopic niche resection (HNR) and expectant management are suitable in women with fertility desire and a niche with a residual myometrium thickness (RMT) ≥ 2.5 mm. Study design: This retrospective cohort study was conducted at International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China between September 2016 and December 2021. We reported the fertility outcomes between women (with fertility desire and a niche with RMT ≥ 2.5 mm) who received HNR or expectant management. Results: We studied 166 women, of whom 72 accepted HNR and 94 accepted expectant management. The HNR group included more symptomatic women, in terms of postmenstrual spotting or infertility. No differences were found regarding niche measures before treatment. The live birth rate was comparable in both groups (HNR versus expectant management as 55.5% versus 45.7%, risk ratio = 1.48, 95% Cl 0.80–2.75, p = 0.21). The pregnancy rate was higher in HNR group than that in expectant management group (n = 72.2% versus n = 56.4%, risk ratio = 2.01, 95% CI 1.04–3.88, p = 0.04). In a subgroup of women with infertility before entry in the study, HNR resulted in a significant higher live birth rate (p = 0.04) and pregnancy rate (p = 0.01). Conclusion: In women with infertility with a symptomatic niche with RMT ≥ 2.5 mm, HNR may be superior to expectant management. This retrospective cohort biased selection against a randomized study, our results still need to be validated in the future with larger clinical multicenter randomized controlled trials

Comparing levonorgestrel intrauterine system with hysteroscopic niche resection in women with postmenstrual spotting related to a niche in the uterine cesarean scar: a randomized, open-label, controlled trial

Background: Postmenstrual spotting and chronic pelvic pain after cesarean delivery are associated with the presence of niches. Levonorgestrel intrauterine system (52 mg) and hysteroscopic niche resection have been shown to relieve niche-related symptoms at 6 months after the intervention. Objective: This trial aimed to compare the effectiveness of 52-mg levonorgestrel intrauterine system with that of hysteroscopic niche resection in reducing niche-related postmenstrual spotting. Study Design: This randomized, open-label, controlled trial was conducted at a medical center in Shanghai, China. Women with symptoms of postmenstrual spotting after cesarean delivery, with a niche depth of at least 2 mm and residual myometrium of at least 2.2 mm on magnetic resonance imaging, and no intention to conceive within the next year were randomly assigned to receive treatment with 52-mg levonorgestrel intrauterine system or hysteroscopic niche resection. The primary outcome was the reduction in postmenstrual spotting at 6 months after randomization, defined as the percentage of women with a reduction of at least 50% in spotting days relative to baseline. Efficacy and safety were assessed using intention-to-treat analysis. Results: Between September 2019 and January 2022, 208 women were randomized into the levonorgestrel intrauterine system group (N=104) or the hysteroscopic niche resection group (N=104). At the 6-month follow-up, a 50% reduction in spotting had occurred in 78.4% (80/102) of women in the levonorgestrel intrauterine system group and in 73.1% (76/104) of women in the hysteroscopic niche resection group (relative risk, 1.07 [95% confidence interval, 0.92–1.25]; P=.370). Spotting decreased over time (Ptrend=.001), with a stronger reduction observed in the levonorgestrel intrauterine system group (P=.001). There was also a significant interaction between time and treatment (P=.007). From 9 months onward, a more significant reduction in spotting was observed in the levonorgestrel intrauterine system group than in the hysteroscopic niche resection group (9 months, 89.2% vs 72.1%; relative risk, 1.24 [95% confidence interval, 1.08–1.42]; 12 months, 90.2% vs 70.2%; relative risk, 1.29 [95% confidence interval, 1.12–1.48]). Moreover, compared with the hysteroscopic niche resection group, the levonorgestrel intrauterine system group had significantly fewer postmenstrual spotting days and total bleeding days from 6 months onward (all P<.001), and less pelvic pain from 3 months onward (all P<.010). No intervention-related complications were reported in any group. During follow-up, 11 (10.8%) women reported hormone-related side effects, and 2 women (2.0%) in the levonorgestrel intrauterine system group had spontaneous partial expulsion. Meanwhile, 3 unintended pregnancies were reported in the hysteroscopic niche resection group. Conclusion: In women with niche-related postmenstrual spotting, the levonorgestrel intrauterine system was not more effective than hysteroscopic niche resection in reducing the number of spotting days by at least 50% at 6 months. However, the levonorgestrel intrauterine system was superior in reducing spotting from 9 months onward, and it reduced the absolute number of spotting days from 6 months onward and pelvic pain from 3 months onward

Diabetic (db/db) mice promoted CUP-1 xenograft growth.

<p>CUP-1 cells were injected subcutaneously into the scruff of diabetic db/db mice and non-diabetic control littermates (m+/db) of 10 weeks age. Tumor size was monitored every other day for 2 weeks and tumor volume was calculated as in nude mice. <b>(A)</b> CUP-1 tumor growth in db/db and m+/db mice. Each point represents mean ± S.E.M (n = 10). <b>(B</b>) Representative photographs show db/db (right) and m+/db mice (left) with respective representative excised tumors on day 27 after CUP-1 inoculation. Arrows indicate the site with CUP-1 inoculation. <b>(C)</b> Representative photomicrographs of H&E-stained CUP-1 tumor tissues from db/db (left) and m+/db mice (right) excised on day 27 after CUP-1 inoculation, X400. Atypical cells with large irregular nuclei (stars) and mitotic figures (arrows) were present in CUP-1 tumor tissues. <b>(D)</b> Western blotting confirmed E7 expression in CUP-1 excised xenograft from both db/db and m+/db mice.</p

CUP-1 cells were tumorigenic in athymic (nu/nu) mice.

<p>Ten million CUP-1 cells were injected subcutaneously into the scruff of 10-week-old nude mice and tumour development was monitored for 12 weeks. <b>(A)</b> Representative image of a nude mouse with significant tumor mass growth (arrow) at week 12 upon CUP-1 inoculation. <b>(B)</b> Representative excised tumors at 12 weeks after inoculation. <b>(C)</b> CUP-1 xenograft growth in nude mice. Tumor volumes were monitored every other day over the study period by caliper measurement of the largest dimension of the tumor, “a” and the perpendicular diameter, “b”. Tumor volumes were calculated using the formula (a×b²) × 0.5236. Each point represents mean ± S.E.M (n = 10). <b>(D)</b> (i) and (ii) Representative photomicrographs of H&E-stained CUP-1 tumor tissues excised from nude mice, X200. Tissue sections showed presence of cells with enlarged and pleomorphic nucleus (black arrowhead), mitotic figures (black circle) and infiltration of red blood cells (black arrow).</p

CUP-1 was an immortalized epithelial cell line with functional E7 protein.

<p><b>(A)</b> Phase-contrast micrograph of CUP-1 cells, (i) x40 (ii) x200. <b>(B)</b> Proliferation profile of CUP-1. CUP-1 was plated at a density of 2 × 10⁵ cells in a T25 flask. When they reached 80% confluency, cell number was determined and cells were subcultured. Each sub-culture was counted as one passage. This process was repeated up to 200 days with over 60 passages. Cumulative population doublings was calculated using the equation: 3.32 x [log(the number of cell harvested)–log(the initial number of cells plated) + S, where S is the initial population doubling. Cumulative population doubling was then plotted against days in culture. Each point represents the mean of triplicate determinations. CUP-1 grew in a steady rate without any sign of senescence, indicating that it was immortalized. <b>(C)</b> Cell type of CUP-1 at passage 28 (P28) and 60 (P60) was characterized via (i) Western blotting and (ii) immunofluorescence using keratinocyte marker pan-keratin (green) and fibroblast marker S100A. HaCaT (keratinocytes) and NIH 3T3 (fibroblasts) were included as cell type controls. CUP-1 nuclei was counterstained by DAPI (blue) in immunofluorescence. <b>(D)</b> Western blot analysis of pRb levels in CUP-1. Total cell lysate was collected from non-transfected primary baby mouse kidney (BMK) cells and CUP-1 cells at P28 and P60. CUP-1 expressed E7 and readily degraded pRb in both P28 and P60. β-actin was included as the loading control.</p