Analysis of related factors influencing postoperative recurrence of adenomyosis treated with HIFU.

OBJECTIVE: To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors. METHODS: Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients' age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia. RESULTS: Among the 308 patients, 238 (77%) were followed up from 6 to 36 months, with an average follow-up time of 15.24 ± 9.97 months. The other 70 (23%) were lost to follow-up. At 6-month after surgery, efficacy rates of dysmenorrhea and menorrhagia management were 86.7% and 89.3%, respectively. Postoperative recurrence rates were 4.8% (1-12 months), 9.0% (12-24 months), and 17.0% (24-36 months) for dysmenorrhea; and 6.3% (1-12 months), 2.4% (12-24 months), and 12.2% (24-36 months) for menorrhagia. Multivariate logistic regression analyses showed that parity (P = 0.043, OR = 1.773, 95% CI 1.018-3.087), uterine size (P = 0.019, OR = 1.004, 95% CI 1.001-1.007), combined treatment of TCM (P = 0.047, OR = 1.846, 95% CI 1.008-3.381), diffuse lesion type (P = 0.013, OR = 0.464, 95% CI 0.254-0.848) and ablation rate (P = 0.015, OR = 0.481, 95%CI 0.267-0.868) were prognostic factors (P < 0.05). Age, course of disease, gravidity, duration of HIFU, duration of irradiation, treatment intensity, preoperative dysmenorrhea score, time of follow-up, western medicine adjuvant therapy, lesion location, and preoperative menstrual volume had no effect on prognosis (P > 0.05). CONCLUSION: HIFU can effectively relieve dysmenorrhea and reduce menstrual volume in patients with adenomyosis. Parity, uterine size, lesion type (diffuse), and ablation rate are risk factors for symptom recurrence after HIFU, while the combination of TCM therapy is a protective factor for relapse. We, therefore, recommend TCM in the adjuvant setting after HIFU according to patient condition.

Efficacy of high-intensity focused ultrasound combined with LNG-IUS for adenomyosis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.

NeiyiKangfu tablets control the progression of endometriosis through inhibiting RAF/MEK/ERK signal pathway by targeting RKIP.

BACKGROUND: NeiyiKangfu tablets (NYKF) are widely used clinically for the treatment of endometriosis (EMS), whose mechanism of action has been extensively studied. Researchers have found that NYKF may control the development of ectopic lesions by inhibiting angiogenesis and inflammatory cytokine secretion. Nevertheless, NYKF's mechanism of action remains unclear. METHODS: In the present study, the function of NYKF in the progression of EMS and the associated underlying mechanism was investigated by in vivo and in vitro experiments. EMS model mice were treated with NYKF and the pro-inflammatory factors and apoptosis of ectopic endometrium as well as RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling activation were assessed. In addition, human endometriosis-derived immortalized entopic stromal (hEM15A) cells transfected with or without RAF kinase inhibitor protein (RKIP)-small-interfering RNA (siRNA) were also treated with NYKF and the proliferation, migration, apoptosis, and RAF/MEK/ERK signaling activation were measured by Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, and western blot, respectively. RESULTS: Results showed that NYKF increased the expression of RKIP, inhibited RAF/MEK/ERK signaling activation, and induced apoptosis while inhibiting proliferation and migration both in EMS mice and hEM15A cells. RKIP knockdown could inhibit the effect of NYKF treatment, leading to the activation of RAF/MEK/ERK signaling and the proliferation and migration of hEM15A cells. CONCLUSIONS: In conclusion, these results suggest that NYKF treatment promotes apoptosis and inhibits proliferation and migration in EMS by inhibiting the RAF/MEK/ERK signaling pathway by targeting RKIP.

ß-Sitosterol Inhibits The Proliferation of Endometrial Cells via Regulating Smad7-Mediated TGF-ß/Smads Signaling Pathway.

OBJECTIVE: To investigate the effect of ß-sitosterol on endometrial cells to understand the underlying mechanism. MATERIALS AND METHODS: This is a laboratory-based experimental study conducted on animals and cells. Histological assays were performed to determine the effect of ß-sitosterol on endometrial cells. The CCK-8 assay was used to assess the inhibitory effect of ß-sitosterol on the proliferation of ectopic endometrial stromal cells (hEM15A). Flow cytometry was performed to evaluate the induction of apoptosis by ß-sitosterol in hEM15A cells. The transwell invasion assay was conducted to measure the suppression of hEM15A cell migration by ß-sitosterol. Western blot analyses were performed to analyze the effect of ß-sitosterol on the expression of Smad family member 7 (Smad7) and the activity of transforming growth factor-ß (TGF-ß1), as well as the phosphorylation of Smad2 and Smad3. RESULTS: Histological assays showed that ß-sitosterol regulates histopathology and induces apoptosis of endometrial cells in vivo. The CCK-8 assay revealed that ß-sitosterol could inhibit the proliferation of hEM15A in human endometriosis patients. Flow cytometry showed that apoptosis was triggered by ß-sitosterol in hEM15A. The transwell invasion assay indicated that the hEM15A migration under the ß-sitosterol treatment group was suppressed. Western blot analyses suggested that ß-sitosterol increased the expression of Smad7, decreased the activity of TGF-ß1, and reduced the phosphorylation of Smad2 and Smad3. The effect of ß-sitosterol was weakened by the silence of Smad7. CONCLUSION: The results suggest that ß-sitosterol can inhibit the proliferation of endometrial cells and relieve endometriosis by inhibiting TGF-ß-induced phosphorylation of Smads through regulation of Smad7.

Efficacy of High-Intensity Focused Ultrasound Combined With GnRH-a for Adenomyosis: A Systematic Review and Meta-Analysis.

Objective: High-intensity focused ultrasound (HIFU) is an innovative non-invasive technology used for adenomyosis. Gonadotropin-releasing hormone agonist (GnRH-a) is a hormone commonly used for adenomyosis. We investigated and assessed the efficacy of HIFU combined with GnRH-a for adenomyosis. Methods: For this systematic review and meta-analysis, we searched Pubmed, Cochrane Library, Web of Science, Embase, CNKI, WanFang, and VIP databases for relevant articles published in Chinese or English that compared HIFU combined with GnRH-a vs. HIFU alone in patients with adenomyosis. The last literature search was completed on January 31, 2021. Two reviewers independently assessed study eligibility and assessed risk of bias. Another two reviewers extracted the data. The RevMan5.3 software was used for the data analysis. Changes in volume of the uterine and adenomyotic lesion were defined as the primary outcomes. The secondary outcomes were visual analog scale (VAS) scores for dysmenorrhea, menstrual volume scores, serum CA125 levels, and recurrence rate. This study is registered with PROSPERO (CRD42021234301). Results: Three hundred and ninety potentially relevant articles were screened. Nine studies with data for 766 patients were finally included. Compared with the HIFU alone group, the HIFU combined with GnRH-a group had a higher rate of uterine volume reduction (MD 7.51, 95% CI 5.84-9.17, p < 0.00001), smaller adenomyotic lesion volume (MD 4.11, 95% CI 2.93-5.30, p < 0.00001), lower VAS score for dysmenorrhea (MD 1.27, 95% CI 0.54-2.01, p = 0.0007) and menstrual volume score (MD 0.88, 95% CI 0.73-1.04, p < 0.00001), and lower CA125 level (SMD 0.31, 95% CI 0.05-0.56, p = 0.02) after the procedure. The recurrence rate in the HIFU combined with GnRH-a group was lower than that in the HIFU alone group (RR 0.28, 95% CI 0.10-0.82, p = 0.02). Conclusions: Compared with HIFU treatment alone, HIFU combined with GnRH-a for the treatment of adenomyosis has greater efficacy in decreasing the volumes of the uterine and adenomyotic lesions and alleviating symptoms. However, since the number of the included studies was too small and most of them were written in Chinese, this conclusion needs to be referenced with caution. And the long-term evidence of its efficacy is still insufficient. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ identifier [CRD42021234].