Reduced expression of SMAD7 and consequent reduction of autophagy promotes endometrial stromal-myofibroblast transition and fibrosis.

Abnormal autophagy and the transforming growth factor-ß (TGFß)-SMAD3/7 signaling pathway play an important role in the development of intrauterine adhesions (IUAs); however, the exact underlying mechanisms remain unclear. In this study, we used IUA patient tissue and SMAD7 conditional knockout mice to detect whether SMAD7 effected IUA via regulation of autophagy and the TGFß-SMAD3 signaling pathway. We applied a combination of techniques for the detection of p-SMAD3, SMAD7, autophagy and fibrosis-related proteins, autophagic flux, and analysis of the SMAD3 binding site. Endometrial tissue of patients with IUA exhibited lower expression levels of SMAD7. In endometrial stromal cells, silencing of SMAD7 inhibited autophagic flux, whereas overexpressed SMAD7 promoted autophagic flux. This SMAD7-mediated autophagic flux regulates the stromal-myofibroblast transition, and these phenotypes were regulated by the TGFß-SMAD3 signaling pathway. SMAD3 directly binds to the 3'-untranslated region of transcription factor EB (TFEB) and inhibits its transcription. SMAD7 promoted autophagic flux by inhibiting SMAD3, thereby promoting the expression of TFEB. In SMAD7 conditional knockout mice, the endometria showed a fibrotic phenotype. Simultaneously, autophagic flux was inhibited. On administering the autophagy activator rapamycin, this endometrial fibrosis phenotype was partially reversed. The loss of SMAD7 promotes endometrial fibrosis by inhibiting autophagic flux via the TGFß-SMAD3 pathway. Therefore, this study reveals a potential therapeutic target for IUA.

Changes in vaginal microbiome after focused ultrasound treatment of high-risk human papillomavirus infection-related low-grade cervical lesions.

BACKGROUND: In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. METHODS: This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. RESULTS: After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000). CONCLUSIONS: The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. TRIAL REGISTRATION NUMBER:  This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

High-intensity focused ultrasound as a pretreatment combined with hysteroscopic resection for gestational trophoblastic neoplasia with chemotherapy intolerance: a case report.

BACKGROUND: Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility. CASE PRESENTATION: A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (ß-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up. CONCLUSION: Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility.

Pregnancy outcomes following ultrasound-guided high-intensity focused ultrasound in submucous leiomyomas: a retrospective study.

OBJECTIVE: To investigate the impact of ultrasound-guided high-intensity focused ultrasound (USgHIFU) on pregnancy in submucous leiomyomas. MATERIALS AND METHODS: Between October 2015 and October 2021, a retrospective observational study was conducted at the Affiliated Hospital of North Sichuan Medical College, China, for 32 women with submucous leiomyomas who became pregnant after USgHIFU. Pregnancy outcomes, submucous leiomyomas characteristics, and USgHIFU parameters were analyzed. RESULTS: A total of 17 (53.1%) deliveries were successfully achieved, with full-term delivery in 16 (94.1%) patients and preterm delivery in 1 (5.9%). After USgHIFU, the effective volume in the uterus cavity and the volume of submucous leiomyomas shrank in all 32 patients. The median time to achieve pregnancy after USgHIFU was 11.0 months. Before pregnancy, myoma type was downgraded in 13 (40.6%) patients, stable in 10 (31.3%) and upgraded in 9 (28.1%). The vaginal expulsion rate of submucous leiomyomas was 28.1%, with complete expulsion in 3 (9.4%) patients and partial expulsion in 6 (18.8%). After USgHIFU, the size of submucous leiomyomas did not increase in each trimester (all p > 0.05). The high complications rate during pregnancy (7/17, 41.2%) was associated with advanced maternal age, with only one (5.9%) premature rupture of membranes possibly associated with submucous leiomyomas. There were 6 (35.5%) vaginal delivery and 11 (64.7%) cesarean sections. All 17 newborns developed well, with a mean birth weight of 3482 g. CONCLUSIONS: In patients with submucous leiomyomas, pregnancies and full-term deliveries can be successfully achieved following USgHIFU, with few related complications.

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. METHODS: This retrospective study recruited 57 patients aged 20-40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. RESULTS: During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46-6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. CONCLUSION: FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy.

BACKGROUND: The reported recurrence rate of endometrial polyps (EPs) after hysteroscopic polypectomy varied widely, and the factors influencing the recurrence of EPs are still controversial. Furthermore, the known definite independent risk factors are almost unchangeable, such as the number of EPs and previous polypectomy history. The aim of this study was to evaluate the impact of chronic endometritis (CE) on the recurrence of EPs in premenopausal women who underwent hysteroscopic polypectomy. METHODS: A retrospective study was conducted at a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence were excluded, including endometriosis and previous polypectomy history. A total of 233 women were enrolled in this study, including 64 (27.5%) cases with CE and 169 (72.5%) cases without CE. CE was diagnosed via immunohistochemical detection of CD138 on the endometrial specimen. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. RESULTS: The recurrence rates of EPs at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8-37.4%) and 9.5% (95% CI 5.0-14.0%), respectively, with an overall recurrence rate of 14.2% (95% CI 9.7-18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P = 0.001). Similarly, the recurrence rate of EPs was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6 and 9 months). CE and multiple EPs were risk factors for EPs recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of EPs. CONCLUSIONS: CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE during hysteroscopic polypectomy was needed. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence.

Application value of contrast-enhanced ultrasonography in the treatment of uterine fibroids by high-intensity focused ultrasound ablation: A retrospective study.

PURPOSE: To determine efficacy and safety of contrast-enhanced ultrasonography (CEUS) in high-intensity focused ultrasound (HIFU) ablation of uterine fibroids (UFs). METHODS: We retrospectively reviewed women undergoing HIFU ablation for UFs between June 2018 and January 2020. Before and after HIFU, patients underwent CEUS and magnetic resonance imaging (MRI) examinations. The relationship between CEUS features and ablation rate was analyzed. The time-intensity curves on CEUS were measured before and after HIFU ablation, and compared with those obtained using MRI. Adverse reactions were recorded. RESULTS: A total of 64 patients were included. The immediate HIFU ablation rate significantly differed between low-, iso-, and high-enhancement UFs (87.2% ± 1.6%, 83.3% ± 2.1%, and 72.9% ± 3.1%, respectively; p < 0.05). On CEUS, the peak time of the time-intensity curve was significantly longer after treatment than before treatment (32.2 ± 9.7 and 26.7 ± 9.4 s, respectively; p < 0.05). Peak intensity was significantly lower after treatment than before treatment (13.7 ± 7.5 and 30.9 ± 11.2 dB, respectively; p < 0.05). All measurements were comparable between CEUS and MRI. The most common peri- and post-procedure adverse reaction was pain, which was temporary. CONCLUSION: CEUS could dynamically and safely evaluate the immediate effects of the HIFU ablation of UFs.

Analysis of clinical outcomes of vitrified-warmed embryo transfer after IVF/ICSI at high altitude (3650 m) in Tibet.

RESEARCH QUESTION: What are the pregnancy outcomes of IVF vitrified-warmed embryo transfer (IVF-FET) carried out in a clinical setting located at an altitude of 3650 m in Tibet, China? DESIGN: A retrospective analysis of 238 infertility couples (n = 344 treatment cycles) who underwent FET treatment at the Xizang Fukang Hospital, Tibet. The overall clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate and ectopic pregnancy rate were statistically analysed. Women were categorized into two groups based on age: 35 years or younger (n = 265 cycles) and over 35 years (n = 79 cycles). The general characteristics and pregnancy outcomes were compared between the two groups. RESULTS: The clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and ectopic pregnancy rate of the 344 FET cycles were 43.02%, 30.90%, 35.17%, 18.24% and 1.35%, respectively. The clinical pregnancy rate (46.04% versus 32.91%), implantation rate (33.92% versus 21.01%) and live birth rate (38.11% versus 25.32%) in the group aged 35 years or younger were significantly greater than those in the group aged over 35 years (P = 0.039, P = 0.004, P = 0.037). The miscarriage rate (17.21% versus 23.08%) and ectopic pregnancy rate (0.82% versus 3.85%) were not significantly different in the two groups. CONCLUSION: A live birth rate of 35.17% can be achieved with IVF-FET in high-altitude areas (3650 m above sea level). Maternal age is still an important determinant of clinical pregnancy rate, implantation rate, and live birth rate of infertile patients in high-altitude areas.

Focused ultrasound for high-risk human papillomavirus infection-related low-grade cervical lesions: a prospective cohort study.

OBJECTIVES: To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL). METHODS: Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated. RESULTS: No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75-21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83-15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1-3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1-6). CONCLUSIONS: For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

Long-term outcome of ultrasound-guided focused ultrasound ablation for gestational trophoblastic neoplasia in the cesarean scar: a case report.

BACKGROUND: The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility. CASE PRESENTATION: A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up. CONCLUSION: Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding.

Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study.

BACKGROUND: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs). METHODS: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed. RESULTS: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment. CONCLUSION: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment.

Therapeutic efficacy of clomiphene citrate combined with metformin in patients with polycystic ovary syndrome.

WHAT IS KNOWN AND OBJECTIVE: Although several clinical trials have compared the clinical efficacy of clomiphene citrate (CC) combined with metformin (MET) in the treatment of women with polycystic ovary syndrome (PCOS), the results are controversial. Therefore, this study was designed to conduct a pooled analysis to evaluate the efficacy of CC combined with MET versus CC in these patients. METHODS: Computerized searches of the PubMed, Web of Science, Embase and Cochrane Library databases were conducted to identify eligible randomized controlled trials (RCTs) from the data obtained up to June 2021. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias in individual RCTs, and RevMan 5.4 was used for data statistical analysis. RESULTS AND DISCUSSION: A total of 13 RCTs were included in the meta-analysis. These studies involved 1,353 patients, 707 of these were in the combination group and 646 in the monotherapy group. The results indicated a higher clinical pregnancy rate (risk ratio [RR] 1.28, 95% confidence interval [CI] 1.06-1.54, p = 0.01) in the combined group compared to the monotherapy group. However, no significant differences were observed in the ovulation rate (RR 1.13, 95% CI 0.98-1.30, p = 0.10), live birth rate (RR 1.13, 95% CI 0.89-1.42, p = 0.32), multiple pregnancy rate (RR 0.58, 95% CI 0.19-1.73, p = 0.33) and abortion rate (RR 1.26, 95% CI 0.86-1.84, p = 0.23) between the two groups. WHAT IS NEW AND CONCLUSION: CC combined with MET has an advantage in improving the clinical pregnancy rate compared to CC alone; however, there is no significant difference in the rate of ovulation. For better management of PCOS, a high-quality RCT is needed to demonstrate the safety of the combination.

Effectiveness of focused ultrasound for high risk human papillomavirus infection-related cervical lesions.

OBJECTIVE: The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. METHODS: A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. RESULTS: The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24-6.76) in the FU group and 26.00 months (95% CI: 22.32-29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840-6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). CONCLUSION: FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

The effect of ultrasound-guided high-intensity focused ultrasound treatment for cesarean scar pregnancy on ovarian reserve.

OBJECTIVE: The aim of this study was to evaluate changes in anti-Müllerian hormone (AMH) levels after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment of cesarean scar pregnancy (CSP). METHODS: A retrospective case series study was conducted in the Affiliated Hospital of North Sichuan Medical College. Thirty-two women with cesarean scar pregnancy who met the inclusion criteria were enrolled in the study between January 2018 and December 2019. All patients underwent USgHIFU treatment with or without suction curettage. Intraoperative blood loss in suction curettage and hysteroscopy procedures, time to return of ß-human chorionic gonadotropin (ß-hCG) to normal levels, and time to recovery of normal menstruation were recorded. AMH levels before and 3 months after HIFU treatment were compared to determine whether USgHIFU treatment affected ovarian reserve. RESULTS: AMH levels before and 3 months after HIFU ablation were 1.87 ± 1.19 ng/ml and 1.90 ± 1.17 ng/ml, respectively. There was no significant difference in AMH levels between the two-time points (p > .05). The median volume of intraoperative blood loss was 20 ml, the median time for the serum ß-hCG level to return to normal was 35.5 days, and the median time of menstruation recovery was 39 days. CONCLUSIONS: USgHIFU treatment for CSP was effective and safe without affecting ovarian reserve.

Comparison of outcomes of hysteroscopic myomectomy of type 2 submucous fibroids greater than 4 cm in diameter via pretreatment with HIFU or GnRH-a.

OBJECTIVE: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) and gonadotropin-releasing analogues (GnRH-a) as pretreatments for the hysteroscopic transcervical resection of myoma (TCRM) for type 2 submucosal fibroids greater than 4 centimeters in diameter. MATERIALS AND METHODS: Seventy-nine patients were assigned into two groups according patient preference: 42 in HIFU and 37 in GnRHa. TCRM was performed after 3 months of pretreatment with HIFU or GnRHa. RESULTS: Following pretreatment with HIFU or GnRHa, uterine-fibroid symptom (UFS) scores and hemoglobin levels (HGB) showed improvement. The fibroid maximum diameter, size of fibroids, and volume of the uterus were decreased. Following HIFU pretreatment, one case reported complete vaginal fibroid expulsion, and four reported partial fibroid expulsion. No similar cases were found in the GnRHa group. Eighteen patients were lost to follow-up prior to TCRM. Among the 31 patients in HIFU, the fibroids were downgraded to type 0 in 10 cases and type 1 in 5 cases. Of the 30 patients in GnRHa, the treated fibroids were downgraded to type 1 in 9 cases. The mean operation time and intraoperative blood loss of the HIFU group were significantly lower than those in the GnRHa group. No significant differences were observed in the incidence of intraoperative complications and the one-time resection rate of fibroids between the two groups (p>.05). CONCLUSIONS: HIFU seems to be superior to GnRHa as a pretreatment method prior to TCRM for type 2 submucosal fibroids greater than 4 centimeters in diameter.

High-intensity Focused Ultrasound for Treatment of Type 2 Submucous Myomas More Than 4 Centimeters in Diameter Prior to Hysteroscopic Myomectomy.

STUDY OBJECTIVE: To assess the feasibility of treating type 2 submucous myomas more than 4 cm in diameter with high-intensity focused ultrasound (HIFU) prior to hysteroscopic myomectomy (HM). DESIGN: Retrospective case series evaluating HIFU treatment of type 2 submucous myomas before HM, with efficacy compared with baseline (i.e., before treatment). SETTING: Teaching hospital. PATIENTS: Five women with type 2 submucous myomas more than 4 cm in diameter (mean, 5.6 cm; range, 4.7-6.3 cm). The mean age of the patients was 40.6 years (31-47 yr); median age 42 years. INTERVENTIONS: Type 2 submucous myomas were treated with HIFU. HM was performed in one step. MEASUREMENTS AND MAIN RESULTS: The time between HIFU and HM was 136 days. The mean volumes of the corpora and myomas were significantly less after HIFU. The mean shrinkage of the corpora and myomas (volume before HIFU/volume before HM × 100%) were 41.4 ± 18.1% and 67.6 ± 17.0%, respectively, which did not differ statistically. All 5 of the submucous myomas changed from type 2 to type 1 or type 0 after HIFU treatment. The percentage of the uterine cavity occupied by the myoma at baseline and after HIFU was 38.8% ± 2.8% and 78.0 ± 21.4%, respectively, a significant increase associated with HIFU. The hemoglobin increased with HIFU, significantly with an elevated value of 11.0 ± 7.5. CONCLUSION: Treatment of type 2 submucous myomas more than 4 cm in diameter with HIFU before HM was effective, with reductions in myoma type (from 2 to 1 or 0) and shrinkage of myoma size. HIFU as a pretreatment should increase the safety of HM.

Effects of short-term mindfulness-based training on executive function: Divergent but promising.

Mindfulness-based training (MBT) has repeatedly been proven effective in improving mental health, as well as in eliciting advantages in executive functions (EFs), as demonstrated by objective measures. However, few studies have discussed the role MBT plays in increasing EFs over short periods of time. This current review, to our knowledge, is the first study to investigate the effect of short-term MBT on EFs. In this case, 14 studies were eventually included after literature screening using PubMed, MEDLINE, Elsevier, Embase, EBSCO and references from retrieved articles. We found that the relationship between short-term MBT and three main components of EFs were found controversial. Some reported that individuals' inhibition, working memory and attention shifting were significantly improved by short-term MBT, whereas others reported no such strong connections between MBT and EFs. These controversial findings result from the use of varied assessment instruments, cognitive tasks and experimental materials. Nonetheless, the findings from this review suggest short-term MBT could be of great value in improving mental health, which might especially enable the enhancement of individuals' inhibition and updating subfunctions of EFs. These practical evidences could have a strong impact on clinical psychology. However, the lack of consistency across the studies in this review indicated that more standardized and profound studies exploring the effects of short-term MBT on EFs are needed in the future.

Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer.

Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. Expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up-regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development.

Effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound for uterine fibroids: a randomised controlled trial.

OBJECTIVE: To investigate the effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound (HIFU) treatment of uterine fibroids. METHODS: A total of 120 patients with solitary uterine fibroid were randomly assigned into Groups A, B, C and D. Patients in Groups A and B received 1.5 ml of SonoVue, Groups C and D received 1.5 ml of saline before HIFU ablation. HIFU sonication started at 6 min after administration of SonoVue or saline in Groups A and C, whereas it started at 10 min in Groups B and D. On day 1 after HIFU, magnetic resonance imaging was performed. Patients were followed up via phone or clinic visit during the first week after HIFU. RESULTS: No significant difference was observed in terms of age, fibroid location, diameter of fibroids, signal intensity on T2-weighted imaging, or tumour volume among the four groups (p > 0.05). The use of SonoVue significantly shortened the treatment time and sonication time. The sonication start time of 6 min, relative to 10 min, had significant effects on the treatment time and sonication time. The use of intravenous SonoVue followed by HIFU ablation 6 min later significantly increased the rate of significant grey-scale changes (55.9%) and the non-perfused volume ratio (94.2% ± 10.6%). No significant differences were observed in the incidence of intra-procedure and post-HIFU adverse effects among the four groups (p > 0.05). CONCLUSIONS: SonoVue could be safely used to enhance the ablation effects of HIFU treatment of uterine fibroids.

[Establishment of the theory and operation of willing acceptance and commitment therapy].

Mindfulness-based psychotherapy, known as the third-wave cognitive behavior therapy, showed a multi-cultural integration trend. As part of it, willing acceptance and commitment therapy not only took root in the discoveries in the fields of evolutionary psychology and cognitive psychology, but also absorbed the concepts of psychotherapy from Chinese traditional culture. As a result, it regards truth and harmony as the essence of health, proposes a triangle model (health/pain-willing acceptance-striving) to elucidate the mechanism of psychopathology and psychotherapy in theory. Operationally, it contains four principles of psychotherapy, which are as follow: "knowing yourself and others, reaction but adequately, reality as well as harmony, willing acceptance and striving". Furthermore, it proposes eight therapeutic procedures including "understand yourself, recognize suffering, check coping style, keep openness and acceptance, mindfulness and flexibility, live in the moment, clarify the value, and commit action". With these principles and procedures, willing acceptance and commitment therapy aims to fade the neural trace of patients' painful memories, improve their psychological flexibility and rebuild their lifestyles consistent with their values.