Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Study on the safety and efficacy of HIFU in the treatment of VaIN.

PURPOSE: This study aimed to investigate the safety and efficacy of High-Intensity Focused Ultrasound (HIFU) treatment for vaginal intraepithelial neoplasia(VaIN). METHODS: Retrospective analysis was conducted on clinical, pathological, and follow-up data of 43 patients who underwent HIFU treatment for VaIN at Xiangya Third Hospital of Central South University between January 2018 and December 2022. The preliminary efficacy and safety of HIFU in treating VaIN were discussed. RESULTS: The 36 patients were analyzed, and the average age was 50.09 ± 12.06 years, including 24 patients with VaIN I and 12 patients with VaIN II. Five cases had a history of hysterectomy (4 due to cervical lesions, 1 due to hysteromyoma), and 2 cases had conization of cervical intraepithelial lesions (CIN). All 36 cases were complicated by human papillomavirus (HPV) infection, with 3 cases also having grade I-II CIN and undergoing cervical HIFU treatment. All patients successfully completed the HIFU treatment, with an average treatment time of 5.99 ± 1.25 min, treatment power of 3.5 W, and average total treatment dose of 1118.99 ± 316.20 J. Patients tolerated the treatment well, experiencing only slight pain with VAS score of 3. There was a mild postoperative burning sensation, which resolved within approximately 10-20 min. After 6 follow-up visits, 33 patients (91.66%) achieved cure, 1 patient (2.77%) showed persistence, 2 patients (5.55%) exhibited progression, and 27 patients (75%) tested negative for HPV. At 12 months of follow-up, the results were consistent with those of 6 months. No complications occurred during the procedure and the follow-up period. CONCLUSION: HIFU is a safe and effective treatment for VaIN. However, this study had a small sample size, a relatively short follow-up period, and lacked a control group, requiring further investigation.

Correlation between preoperative three-dimensional transvaginal ultrasound and postoperative pregnancy outcomes after hysteroscopic adhesiolysis. / å®«è ”ç²˜è¿žåˆ†ç¦»æœ¯å‰ç»é˜´é“ä¸‰ç»´è¶ å£°æ£€æŸ¥ä¸Žæœ¯åŽå¦Šå¨ ç»“å±€çš„ç›¸å ³æ€§.

OBJECTIVES: Uterine adhesion is mainly caused by endometrial injury, leading to poor postoperative pregnancy outcome. Therefore, preoperative evaluation on uterine cavity, especially endometrial condition, is very necessary. This study aims to explore the correlation between preoperative three-dimensional transvaginal ultrasound (3D-TVS) imaging characteristics and postoperative pregnancy outcomes after hysteroscopic adhesiolysis (HA). METHODS: A total of 401 patients, who underwent HA surgery from February 22, 2018 to October 31, 2018 at the Third Xiangya Hospital of Central South University or Changsha Jiangwan Hospital, were enrolled, and we collected data regarding the preoperative 3D-TVS imaging characteristics and followed up their postoperative pregnancy outcomes. Correlation analysis and univariate and multivariate logistic regression analysis were performed between imaging features and pregnancy outcomes (live and non-live birth outcomes) in patients with intrauterine adhesion. RESULTS: The results of correlation analysis showed that endometrial thickness, endometrial echo, visible tubal openings, endometrial blood flow, intercornual distance, and endometrial peristalsis were correlated with the live birth rate (all P<0.05). Logistic regression analysis revealed that in the HA patients with the live birth, the endometrial thickness was thicker (P<0.001), endometrial echo was more homogeneous (P<0.001), the number of tubal openings was more (P<0.001), the intercornual distance was wider (P<0.05), the endometrial blood flow, and irregular cases of endometrial peristaltic waves were more and cases of deficiency were fewer (both P<0.01) than those in the non-live birth group. CONCLUSIONS: Preoperative 3D-TVS imaging performance is closely related to pregnancy outcomes of HA patients, and preoperative 3D-TVS can be used to predict pregnancy outcomes after HA.

Value and influencing factors of preoperative MRI evaluation for previous cesarean scar defect associated abnormal uterine bleeding in patients undergoing laparoscopic surgery. / æœ¯å‰ç£å ±æŒ¯è¯„ä»·è ¹è ”é•œæ‰‹æœ¯æ²»ç–—å‰–å®«äº§åˆ‡å£ç˜¢ç—•ç¼ºé™·ç›¸å ³å¼‚å¸¸å­å®«å‡ºè¡€çš„ä»·å€¼åŠå½±å“å› ç´ ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: As the cesarean section rate increases year by year, the treatment of previous cesarean scar defects (PCSD) poses a significant challenge. This study aims to evaluate the clinical value of preoperative magnetic resonance imaging (MRI) technology and analyze relevant influencing factors for patients with abnormal uterine bleeding (AUB) associated with cesarean scar defects who underwent laparoscopic surgery. METHODS: A retrospective cohort analysis was performed on women who underwent laparoscopic surgery for PCSD-related AUB at the Department of Gynecology, the Third Xiangya Hospital of Central South University from 2018 to 2022. A total of 57 patients who underwent laparoscopic surgery for the treatment of AUB associated with PCSD were divided into 2 groups based on their postoperative clinical cure status: The clinically-cured group (n=28, 49.1%) and the non-clinically-cured group (n=29, 50.9%). After a postoperative follow-up period of 3 months for all participants, logistic regression analysis was conducted to explore the correlation between the clinical cure rate of AUB associated with cesarean scar defects treated by laparoscopic surgery and various factors. These factors included patient age, clinical symptoms, obstetric history, history of cesarean section, basic clinical information, preoperative MRI parameters, and postoperative menstrual conditions. RESULTS: There were no significant differences in many aspects, including the patient's age at the time of previous cesarean section, number of pregnancy, time since the previous cesarean section, the uterus position assessed by preoperative T2 signal MRI, defect length, defect width, residual muscle layer thickness, adjacent uterine muscle layer thickness, and distance from the defect to the external cervical os between the 2 groups (all P>0.05). However, the time of onset of AUB symptoms (P=0.036, OR=1.019, 95% CI 1.002 to 1.038) and the depth of the defect on the preoperative MRI (P=0.010, OR=5.793, 95% CI 1.635 to 25.210) were identified as risk factors affecting the clinical cure rate. CONCLUSIONS: The time of onset of AUB symptoms and the depth of the defect on preoperative MRI are risk factors that influence the clinical cure rate of laparoscopic surgery for the treatment of AUB associated with PCSD, which could be helpful for evaluating the prognosis of disease.

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients. / é«˜å±åž‹äººä¹³å¤´ç˜¤ç— æ¯’æ„ŸæŸ“æ‚£è€ å®«é¢ˆè„±è½ç»†èƒžJAM3/PAX1é«˜ç”²åŸºåŒ–è¯Šæ–­å®«é¢ˆé«˜çº§åˆ«ç— å˜.

OBJECTIVES: Currently, traditional cervical cancer screening methods, such as high-risk human papillomavirus testing and liquid based cytology (LBC), still possess limitations. This study aims to identify new diagnostic biomarkers to achieve the goal of "precision screening" via exploring the clinical value of DNA methylation [ΔCtP: paired box gene 1 (PAX1)and ΔCtJ: junctional adhesion molecule 3 (JAM3)] detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. METHODS: A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied. Among them, 122 patients had non-high-grade cervical lesions, and 14 patients had high-grade cervical lesions. The variables included general information (age, body mass index, and menopause status), LBC, high-risk human papillomavirus, cervical tissue pathology, vaginal examination results, and the ΔCt values of JAM3 and PAX1 gene methylation. Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions, followed by correlation analysis and construction of a conditional inference tree model. RESULTS: Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group (all P<0.05). Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP (r=-0.36, P<0.001), ΔCtJ (r=-0.448, P<0.001), LBC (r=-0.305, P<0.001), or bacterial diversity (r=-0.183, P=0.037). The conditional inference tree showed that when ΔCtJ>10.13, all of patients had non-high-grade cervical lesions, while ΔCtP>6.22, the number of non-high-grade lesions accounted for 97.5% (117/120), and high-grade lesions accounted for only 2.5% (3/120). When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy (NILM), 105 (99.1%) patients were non-high-grade cervical lesions, only 1 (0.9%) patient was high-grade lesion. When the results of LBC were high-grade lesions, only 9 patients' histopathological examination was the high-grade lesions and 3 non-high-grade lesions. When LBC indicated low-grade lesions, atypical squamous cell of undetermined significance, no intraepithelial lesions, and ΔCtP>6.22, 117 (97.5%) of patients' histopathological examination was the non-high-grade lesions. CONCLUSIONS: The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.

Characterization of Pathogenic CD8+ T cells in Chlamydia-Infected OT1 Mice.

Chlamydia trachomatis is a leading infectious cause of infertility in women due to its induction of lasting pathology such as hydrosalpinx. Chlamydia muridarum induces mouse hydrosalpinx because C. muridarum can both invade tubal epithelia directly (as a first hit) and induce lymphocytes to promote hydrosalpinx indirectly (as a second hit). In the current study, a critical role of CD8+ T cells in chlamydial induction of hydrosalpinx was validated in both wild type C57BL/6J mice and OT1 transgenic mice. OT1 mice failed to develop hydrosalpinx partially due to the failure of their lymphocytes to recognize chlamydial antigens. CD8+ T cells from naive C57BL/6J mice rescued the ability of recipient OT1 mice to develop hydrosalpinx when naive CD8+ T cells were transferred at the time of infection with Chlamydia. However, when the transfer was delayed for 2 weeks or longer after the Chlamydia infection, naive CD8+ T cells no longer promoted hydrosalpinx. Nevertheless, CD8+ T cells from mice immunized against Chlamydia still promoted significant hydrosalpinx in the recipient OT1 mice even when the transfer was delayed for 3 weeks. Thus, CD8+ T cells must be primed within 2 weeks after Chlamydia infection to be pathogenic, but, once primed, they can promote hydrosalpinx for >3 weeks. However, Chlamydia-primed CD4+ T cells failed to promote chlamydial induction of pathology in OT1 mice. This study optimized an OT1 mouse-based model for revealing the pathogenic mechanisms of Chlamydia-specific CD8+ T cells.

RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma.

BACKGROUND: RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. METHODS: Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. RESULTS: A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. CONCLUSION: The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.

Bone marrow mesenchymal stem cells combined with estrogen synergistically promote endometrial regeneration and reverse EMT via Wnt/ß-catenin signaling pathway.

BACKGROUND: Intrauterine adhesion (IUA) is a clinical disease characterized by the uterine cavity occlusion caused by the damage of the endometrial basal layer. Bone marrow mesenchymal stem cells (BMSCs) transplantation have the potential to promote endometrial regeneration mainly through paracrine ability. Estrogen is an indispensable and important factor in the repair of endometrial damage, which has been reported as a promising and adjunctive therapeutic application for stem cell transplantation therapy. This study aims to investigate the synergistic effect of BMSCs and estrogen on improving the endometrial regeneration and restoring the endometrium morphology in a dual damage model of IUA in rabbits and the underlying molecular mechanisms. METHODS: BMSCs were isolated and identified by adipogenic and osteogenic differentiation and flow cytometry assays. The rabbit IUA animal model was established by a dual damage method of mechanical curettage and lipopolysaccharide infection. Additionally, we investigated the therapeutic impact of both BMSCs and estrogen either separately or in combination in a rabbit model. The retention of PKH26-labeled BMSCs was observed by vivo fluorescence imaging.The number of endometrial glands and the degree of fibrosis were observed by H&E and Masson staining respectively. Western blotting, Immunohistochemistry and immunofluorescence staining were performed to detect biomarkers related to endometrial epithelium, endometrial fibrosis and EMT. Finally, the protein expression of core molecules of Wnt/ß-catenin pathway was detected by Western blotting. RESULTS: PKH26-labeled fluorescence results revealed that BMSCs appeared and located in the endometrial glands and extracellular matrix area when orthotopic transplanted into the uterine cavity. Histological assays showed that remarkably increasing the number of endometrial glands and decreasing the area of endometrial fibrosis in the BMSCs combined with estrogen treatment group. Moreover, downregulated expression of fibrosis markers (fibronectin, CollagenI, a-SMA) and interstitial markers (ZEB1, Vimentin, N-cadherin), as well as upregulated E-cadherin expression were found in the combined group. Further study of in vivo staining revealed that fluorescence intensity of CK7 was stronger in the combined group than that of direct BMSCs intrauterine transplantation, while vimentin showed the opposite results. Moreover, the protein levels of ß-catenin, Axin2, C-myc, CycinE of Wnt/ß-catenin signaling pathway increased in the BMSCs combined with estrogen group than in the other treatment groups. CONCLUSION: BMSCs combined with estrogen can promote the differentiation of stem cells into endometrial epithelial cells to facilitate the regeneration of damaged endometrium. The potential mechanism of the synergistic effect may inhibit the occurrence of EMT by activating the Wnt/ß-catenin signaling pathway.

The association between vaginal microbiota disorders and early missed abortion: A prospective study.

INTRODUCTION: The objective of this study was to explore the association between disordered vaginal microbiota and missed abortion to ascertain potential causes of missed abortion related to vaginal microbiology. MATERIAL AND METHODS: This study was a prospective cohort study with a comparison group (reference group). Vaginal secretions from the posterior fornix of women in the early stages of pregnancy were collected in the Xiangya Third Hospital of Central South University in Changsha, Hunan, China, from November 2018 to November 2019. A total of 54 cases of missed abortion (case group) and 50 cases of normal pregnancy requiring induced abortion (reference group) were analyzed. Bacterial DNA was extracted, hybridized with gene-specific primers, and then detected using a bacterial chip. The composition and relative abundance of vaginal microbiota in the two groups were compared using α-diversity analysis, ß-diversity analysis, and the linear discriminant analysis effect size method. RESULTS: The α-diversity analysis showed that the Simpson index of the case group was lower than that of the reference group, whereas the Shannon index in the case group was higher. The relative abundance of Firmicutes in the case group (42.52%) was lower than in the reference group (51.03%, p < 0.05), as was the relative abundance of Lactobacillus (case group 16.51%, reference group 23.00%; p < 0.05). Interestingly, levels of Mycoplasma genitalium and Ureaplasma were lower in the case group (p < 0.05). The relative abundance of Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus gasseri was also significantly lower in the case group than in the reference group (p < 0.05). The pathways enriched in the case group were predominantly related to metabolism, whereas the genetics-related pathways were predominantly enriched in the reference group. CONCLUSIONS: Bacteria are more diverse and unevenly distributed in patients with missed abortion. Decreases in the proportion of vaginal Lactobacillus and changes in Lactobacillus species in these patients may increase the chance of genital tract pathogenic bacterial infection. To our knowledge, our study was the first to observe that a decrease of Firmicutes levels in the vaginal microbiota might impair energy metabolism and have an association with missed abortion.

Management of a multiple endocrine neoplasia type 1 during pregnancy: a case with primary hypertension.

Multiple endocrine neoplasia type 1 (MEN 1) is a rare hereditary disease which transmitted as autosomal dominant disorder with high penetrance. MEN1 includes vary combinations of more than 20 endocrine and non-endocrine tumors. Clinically, MEN1 is characterized by tumor or hyperplasia in two or more endocrine tissues (parathyroid, pituitary, pancreas, adrenal glands). Since it is a rare condition, there are no guidelines with respect to the follow-up of pregnant women with MEN 1, here we the first Asian case of a 32-year-old primigravida with a confirmed diagnosis of MEN1 and primary hypertension prior to conception, cesarean section was performed at 34+2 weeks for severe preeclampsia and potential risks, both the patient and fetus recovered well.

A Novel Nomogram Based on 3-dimensional Transvaginal Ultrasound for Differential Diagnosis Between Severe and Mild-to-Moderate Intrauterine Adhesions.

STUDY OBJECTIVE: To develop and validate a nomogram for differentiating severe intrauterine adhesions (IUAs) from mild-to-moderate IUAs preoperatively on the basis of 3-dimensional transvaginal ultrasound (3D-TVUS). DESIGN: Retrospective observational study. SETTING: University-affiliated hospital. PATIENTS: A dataset of 413 patients who had undergone hysteroscopic adhesiolysis and 3D-TVUS examination before hysteroscopic adhesiolysis between March 2019 and December 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 212 patients with mild-to-moderate IUAs and 201 patients with severe IUAs were enrolled. Intercornual distance, endometrial thickness, number of visible fallopian tubal ostia, echoes of the endometrial-myometrial junction zone, and endometrial blood flow grade differed significantly between the severe and mild-to-moderate IUAs groups. The area under the receiver operating characteristic curve of the nomogram was 0.880 (95% confidence interval, 0.843-0.918) in the training set and 0.878 (95% confidence interval, 0.818-0.939) in the validation set, revealing reliable discrimination. The calibration curve and Hosmer-Lemeshow test showed strong calibration, and decision curve analysis indicated that the nomogram had a high net benefit and a wide range of threshold probabilities. CONCLUSION: This nomogram, which was developed on the basis of 3D-TVUS, can accurately distinguish severe IUAs from mild-to-moderate IUAs preoperatively.

Effect of growth hormone on endometrium growth of intrauterine adhesion and the underlying mechanism. / ç”Ÿé•¿æ¿€ç´ ä¿ƒè¿›å®«è ”ç²˜è¿žå­å®«å† è†œç”Ÿé•¿çš„ä½œç”¨åŠå ¶æ½œåœ¨æœºåˆ¶.

OBJECTIVES: The main treatment for intrauterine adhesion (IUA) is hysteroscopic adhesiolysis (HA), which most of treatment frequently employs estrogen and progesterone cycle therapy. The growth and coverage of endometrium after operation is a difficult problem, and several hospitals in China have performed growth hormone (GH) in empirically treating IUA, which has achieved excellent curative effects. Unfortunately, the mechanism of action has not yet been clearly elucidated. In previous study, an IUA animal model after surgical abortion and curettage in pregnant rats has been successfully established. In this experiment, the IUA animal model after surgical abortion and curettage in pregnant rats, which is more in line with the mechanism of human intrauterine adhesion, was used for the first time to investigate the therapeutic effect of GH on IUA in the pregnant rat curettage model. The expression of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3 (p-STAT3), STAT5 and p-STAT5 content were detected by immunohistochemistry to preliminarily explore the possible mechanism of GH involving in promoting endometrial growth of IUA, and to provide a theoretical basis for clinical medication and treatment. METHODS: Pregnant rats were anesthetized, and the bilateral embryos were removed completely. Then the rat endometrium was scraped with a curette in 4 different directions (front, back, left, and right). After the IUA animal model was established, the rats were randomly divided into 3 groups (n=5): a control group, a GH group, and a GH + AG490 group. Normal saline (0.4 mL/100 g) was injected subcutaneously at the 7th day after curettage in the control group；0.15 U/100 g of GH was injected subcutaneously at the 7th day after curettage in the GH group; 0.15 U/100 g of GH was injected subcutaneously and 1 mg/100 g AG490 was injected intraperitoneally at the 7th day after curettage in the GH+ AG490 group. All the rats were injected continuously for 5 days. The rats in each group were sacrificed at the 14th day. The uterus of rats in each group was stained with HE staining to explore the endometrial morphology and the number of endometrial glands in each group, and Masson staining was utilized to observe the degree of endometrial fibrosis. The levels of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by immunohistochemistry. RESULTS: 1) The number of glands in the GH group was more than that in the control group on the 14th day, with statistical difference (P<0.05). However, the number of endometrial glands in the AG490+GH group was decreased compared with the GH group on the 14th day (P<0.05). 2) The fibrosis ratio in the GH group was less than that in the control group at the 14th day after operation (P<0.05). However, the area of endometrial interstitial fibrosis in the AG490+GH group was much higher than that in the GH group 14 days after operation (P<0.05). 3) Compared with the control group, there was not significant difference in the levels of STAT3 and STAT5 in GH group (both P>0.05), while the levels of protein p-STAT3 and p-STAT5 were increased in the GH group (both P<0.05). Compared with the GH group, there was not significant difference in the levels of STAT3 and STAT5 in the AG490+GH group (both P>0.05), while the levels of p-STAT3 and p-STAT5 were decreased in the AG490+GH group (both P<0.05). CONCLUSIONS: GH can not only promote the growth of endometrial glands in the IUA model, but also reduce the degree of fibrosis and play a role in the treatment of IUA, which may be related to the activation of the Janus kinase (JAK), JAK/STAT3 and STAT5 signaling pathways.

Diagnosis of septate uterus. / 纵隔子宫的诊断（英文）.

The septate uterus is the most common structural uterine anomalies and it is associated with the poor reproductive outcome. It is believed to be the result of the failure in resorption of the tissue connecting the 2 paramesonephric ducts prior to the 20th embryonic week. The true prevalence of uterine septum is difficult to ascertain, as many uterine septal defects are asymptomatic. The septate uterus is usually diagnosed during an infertility evaluation and affects reproductive health by impairing fertility and increasing adverse pregnancy outcomes. The variations in uterine and cervical/vaginal anomalies collectively referred to as Müllerian anomalies. No consistent gold standard for the diagnosis of Müllerian anomalies exists. The preferred diagnostic method for Müllerian anomalies is two-dimensional ultrasound, other methods such as three-dimensional ultrasound, magnetic resonance imaging, hysterosalpingo contrast sonography, hysterosalpingography, hysteroscopy, and laparoscopy are also used to improve accuracy.

Treatment of septate uterus. / 纵隔子宫的治疗（英文）.

Although there is insufficient evidence supporting the link between septate uterus and infertility, there are many studies demonstrated the effect of spetal incision on pregnancy in women diagnosed with septate uterus associated with infertility. Hysteroscopic metroplasty can significantly improve the reproductive performance of those with septate uterus. Some Müllerian malformations can be healed by surgery. The accurate diagnosis and appropriate therapeutic approch are fundamental for successful treatment. Any attempt at surgical correction of uterine abnormalities must be aimed at preserving or improving reproductive function. Among congenital uterine anomalies, septate uterus is the most amenable to simple hysteroscopic treatment. The resection of the septum is performed as standard treatment worldwide.

Chinese medicine Yangmo decoction ameliorates intrauterine adhesion prognosis following hysteroscopic adhesiolysis. / ä¸­è¯å »è†œæ–¹æ”¹å–„å®«è ”é•œä¸‹å®«è ”ç²˜è¿žåˆ†ç¦»æœ¯åŽå®«è ”ç²˜è¿žçš„é¢„åŽ.

OBJECTIVES: Hysteroscopic adhesiolysis (HA) remains the mainstay on treatment for intrauterine adhesions (IUA). The fertility outcome of patients with moderate and severe intrauterine adhesions after HA is still far from satisfactory. Estrogen combined with progesterone is the most common treatment; however, they do not help in improving the fertility rate to the maximum because of the limitations. This retrospective, non-randomized controlled study will assess the effects of traditional Chinese medicine Yangmo decoction after HA in restoration of the endometrium and improvement of the fertility rate. METHODS: A total of 427 patients, who met the inclusion criteria, aged between 20 and 45 years and diagnosed with moderate or severe IUA underwent HA at the Third Xiangya Hospital from January to August 2021, were enrolled for this study. Participants were assigned into 2 groups: A Yangmo decoction group (n=213, patients were given Yangmo decoction consisting of Ginseng flower, Sanchi flower, Daidai flower, Snow lotus, Licorice and so on after HA), and an estrogen and progesterone group (n=214, patients were given estrogen and progesterone after HA). The following basic information was collected retrospectively for both groups, including age, parity, history of abortion, menstrual status, and times of hysteroscopic interventions. American Fertility Society (AFS) score was used by a senior surgeon and the density of opening of endometrial glands was evaluated during HA. The parameters were obtained from three-dimensional transvaginal ultrasound (3D-TVUS) preoperatively and postoperatively, to evaluate the efficacy of Yangmo decoction, estrogen, and progesterone. All patients were followed up on telephone to determine the fertility rate until 6 months from the last HA. RESULTS: Based on the basic information collected preoperatively, there were no significant differences between the groups (all P>0.05). Postoperatively, patients in the Yangmo decoction group had a better surgical success rate with a more significant AFS reduction (P<0.001), better density of opening of endometrial glands in the uterine cavity (P<0.000 1) after HA, and a better fertility rate (40.4%) in the time of 6 months after the last HA than those of the estrogen and progesterone group. CONCLUSIONS: Yangmo decoction has better therapeutic efficacy in the treatment of intrauterine adhesion after HA than the combined effect of estrogen and progesterone. Yangmo decoction helps restore the endometrium and improve the fertility rate, therefore, it can be adopted as a routine practice for IUA patients who have fertility requirements.

Value of transvaginal three-dimensional ultrasound in evaluating the curative effect of Yangmo decoction in the treatment of uterine adhesion. / ç»é˜´é“ä¸‰ç»´è¶ å£°åœ¨åˆ¤æ–­å »è†œæ–¹æ²»ç–—å®«è ”ç²˜è¿žæ•ˆæžœä¸­çš„ä»·å€¼.

OBJECTIVES: Intrauterine adhesions (IUA) is the damage of the basal layer of the endometrium caused by various reasons, resulting in adhesion of the uterine muscle walls to each other, which is manifested as clinical symptoms such as spanomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis (HA) is the main treatment, for patients with moderate or severe adhesion or angular adhesion, the incidence of postoperative adhesion is high. Traditional Chinese medicine "Yangmo decoction" can promote endometrial growth. Three-dimensional transvaginal ultrasonography (3D-TVUS) can judge IUA and evaluate uterine receptivity through three-dimensional imaging. This study aims to investigate the value of 3D-TVUS in judging the efficacy of Yangmo decoction in the treatment of intrauterine adhesions. METHODS: The clinical data of patients who underwent HA at two different centers in department of Gynecology of Third Xiangya Hospital of Central South University and Changsha Jiangwan Hospital from January 2021 to August 2021 were retrospectively collected. A total of 275 eligible patients were included. According to the postoperative management measures, the selected patients were divided into two groups. Yangmo decoction group (n=138): the use of Yangmo decoction and uterine-shaped silicon stent post HA; Hormone group (n=137): the use of estrogen, progesterone and uterine-shaped silicon stent post HA. The preoperative general data, preoperative and postoperative 3D-TVUS parameters of the two groups were analyzed. RESULTS: The endometrial thickness of Yangmo decoction group was thicker than that of hormone group (P<0.001), the intercornual distance was wider (P=0.016), the endometrial echo was more homogeneous (P=0.018), the percentage of bilaterally visible tubal opening was higher (P<0.001), the endometrial morphology was better (P=0.012), and endometrial blood flow, endometrial motility and uterine motion were better in Yangmo decoction group than that in the hormone group (all P<0.001). CONCLUSIONS: The endometrial thickness, echo, blood flow, and peristalsis, the number of visible tubal opening, uterine motion, and the intercornual distance obtained by 3D-TVUS examination are important factors to evaluate the prognosis of postoperative drug treatment for IUA. 3D-TVUS is of great significance in evaluating the efficacy of Yangmo decoction in the treatment of IUA.

Preliminary study on the advantages of hysteroscopic myomectomy with cold knife. / å®«è ”é•œä¸‹å†·åˆ€åˆ‡é™¤é»è†œä¸‹è‚Œç˜¤ä¼˜åŠ¿çš„åˆæ­¥æŽ¢è®¨.

OBJECTIVES: At present, hysteroscopic submucosal fibroids resection is mostly performed by hysteroscopic electric resection (hereinafter referred to as electric knife). During the operation, the electrothermal effect could not only damage the endometrial tissues covered by the surface of the fibroid, but also easily damage the endometrial tissues around the fibroid, which is very unfavorable for patients with fertility requirements. In addition, for some special fibroids (located at horn and fundus) or Type II and multiple submucosal fibroids, the traditional electric resection is still very difficult. With the opening of the second-child policy and the urgent desire of patients for fertility, more and more attention is paid to the concept of fertility protection in China. Therefore, hysteroscopic cold knife technology (hereinafter referred to as cold knife) has gradually entered the vision. The cold knife has the advantages of simple operation, such as little trauma and quick postoperative recovery. In this study, the advantages of cold knife in the surgical resection of submucosal fibroids are discussed by comparing the safety and effectiveness between the hysteroscopic cold knife resection (hereinafter referred to as cold knife) and the electric knife resection in the submucosal fibroids. METHODS: The clinical data of 112 patients with submucosal fibroids diagnosed and treated by hysteroscopic surgery at the Third Xiangya Hospital of Central South University from January 2017 to October 2021 were retrospectively analyzed, including preoperative general information (such as age, gravidity, abortion times, the size, location, type and number of submucosal fibroids, preoperative hemoglobin value) and intraoperative conditions [such as intraoperative bleeding, the operation time, residual rates and intraoperative complications (massive bleeding, perforation, water poisoning)]. The patients were divided into a cold knife group and an electric knife group, and there were 40 cases in the cold knife group and 72 cases in the electric knife group. The postoperative complications and the pregnancy outcomes in the 2 groups were followed up by telephone, the follow-up data included postoperative recurrence rate, pregnancy rate, pregnancy mode, and pregnancy outcome. RESULTS: Compared with the electric knife group, the cold knife group had more submucous myomas located in the horn or fundus of the uterus (9.7% vs 25.0%), and more Type II myomas or combined with Type II myomas (26.4% vs 70.0%). However, there were no significant difference in intraoperative bleeding, the operation time, intraoperative complications and the residual rates between the 2 groups (all P>0.05). A total of 98 patients were followed up, including 32 patients in the cold knife group and 66 patients in the electric knife group. Compared with the electric knife group, there were lower postoperative complications in the cold knife group (12.5% vs 37.9%) (P<0.05). Among the 7 patients with multiple submucosal fibroids (the number of fibroids ≥5), there were 4 patients in the electric knife group and 3 patients in the cold knife group. In the electric knife group, the postoperative menstrual volume in the 4 patients was significantly reduced and 3 patients had postoperative fertility requirements, which were all diagnosed as intrauterine adhesion by hysteroscopy and performed further surgery. Later, 2 patients had successful pregnancy, 1 had miscarriage, and 1 had full-term spontaneous labor. However, the menstrual volume of the 3 patients in the cold knife group was not significantly reduced compared with normal menstrual volume, and 2 of them had fertility requirements, and they had natural pregnancy and full term vaginal delivery. There were no significant differences in postoperative recurrence rate, pregnancy rate, pregnancy mode and pregnancy outcome between the 2 groups (all P>0.05). CONCLUSIONS: Both the electric knife and cold knife resection are safe and effective methods for the treatment of submucosal fibroids. Compared with electric knife resection, the cold knife resection has fewer postoperative complications and perhaps more advantages in endometrial protection, especially for the patients with fertility requirements, submucosal fibroids located at the fundus or horn of the uterus, Type II submucosal fibroids, and multiple submucosal fibroids.

Hysteroscopic dilation techniques in hysteroscopic adhesiolysis. / é•œä¸‹æ‰©å®«æ³•åœ¨å®«è ”é•œå®«è ”ç²˜è¿žåˆ†ç¦»æœ¯ä¸­çš„åº”ç”¨.

OBJECTIVES: Intrauterine adhesion (IUA) is mainly caused by intrauterine operations such as pregnancy-related curettage and hysteroscopic surgery, resulting in the trauma to the basal layer of the endometrium. Hysteroscopic adhesiolysis is a crucial step in the comprehensive treatment of IUA, and the most common complication is uterine perforation. More than half of all uterine perforations occur during the hysteroscopy or probe/dilator pass through the internal os. Furthermore, inappropriate surgical procedures may lead to endometrial injury, recurrence or even aggravation of adhesions, and complications such as cervix laceration and false passage formation. This study aims to explore the usage of the hysteroscopic dilatation techniques to dilate the internal os and lower uterine segment, which is via hysteroscopy entering the internal os laterally and swinging, or by directly opening the forceps or scissors and bluntly spreading dissection under direct hysteroscopic vision. By using the hysteroscopic dilatation techniques, we intend to improve the effectiveness and safety of cervical dilation in patients with IUA in the internal os and/or lower uterine segment. METHODS: A total of 282 patients with adhesions in the internal os or lower uterine segment underwent HA in the Third Xiangya Hospital of Central South University from January 2020 to June 2021 were included, ranging from 21 to 46 (33.0±4.8) years old in age and 5 to 12 in the American Fertility Society score. Among them, there were 2 cases of false passage formation caused by traditional dilatation in other hospitals. All patients underwent hysteroscopy with integrated hysteroscopy with 5Fr instrument channel and 4.9 mm outer sheath diameter. The internal orifice of cervix and the lower segment of uterine cavity were dilated under the microscope. After the hysteroscopy entered the uterine cavity, the separation of uterine cavity adhesion and the placement of uterine contraceptive ring or uterine stent into the uterine cavity were performed routinely. Age, surgical records, and surgical videos of all included cases were collected. The success rate of dilation and the incidence of surgical complications were assessed. RESULTS: In all cases, the hysteroscopys successfully entered into the uterine cavity by using the hysteroscopic dilatation techniques without failure and switching to cervical dilators. In the 2 cases of false passage due to previous cervical dilation, the uterine cavity was identified and found successfully under direct hysteroscopic vision. During the whole surgery, the vision was clear, and no complications (such as cervix laceration, false passage formation, uterine perforation or water intoxication) occurred. One to 3 months postoperative hysteroscopy revealed no significant fibrotic stenosis in the internal os and lower uterine segment. CONCLUSIONS: The hysteroscopic dilation techniques are a strategy for separation methods that is following structural hierarchy anatomy in the mode of "see and treat" for the adhesion in the internal os and uterine cavity under direct hysteroscopic vision. This method not only has ultrasound guidance, but also has the judgment of structural hierarchy anatomy under direct hysteroscopic vision, so there is less chance of anatomical level judgment error. This method makes full use of the hysteroscopic judgement of the experienced hysteroscopic surgeons, so that surgeons can timely find and avoid re-entering the old false passage caused by previous surgery. The adhesions in the internal os and lower uterine segment were separated by the hysteroscopic dilation techniques. In this way, the damage to the endometrium caused by forced insertion of the hysteroscopy can be avoided. Meticulous separation of adhesions and cervical dilation under direct hysteroscopic vision can effectively reduce the occurrence of surgical complications such as false passage formation, cervical laceration, and uterine perforation. The use of mini-hysteroscopy eliminates the need for preoperative cervical preparation, avoiding associated risks and side effects. Moreover, for patients with adhesions in the internal os and lower uterine segment, preoperative cervical preparation is not effective in cervical dilation, while the hysteroscopic dilation techniques are effective, with higher patient acceptance due to the absence of preoperative cervical preparation. For the skilled hysteroscopic surgeons, the hysteroscopic dilation technique is easy to operate and worthy of clinical application.

A model established for predicting natural pregnancy possibility based on the imaging characteristics of 4-dimensional hysterosalpingo-contrast sonography. / åŸºäºŽå››ç»´è¶ å£°å­å®«è¾“åµç®¡é€ å½±çš„å½±åƒå­¦ç‰¹å¾å»ºç«‹è‡ªç„¶å¦Šå¨ é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: The incidence of infertility is increasing, more than 30% of them having related abnormal tubal patency. Four-dimensional (4D) hysterosalpingo-contrast sonography (HyCoSy) overcomes the shortcomings of 3D HyCoSy in the diagnosis of tubal patency, showing high specificity and accuracy. In addition, 4D HyCoSy discards iodine allergy and X-ray radiation and possesses easy-operating, contributing to good acceptance in clinical practice. However, there is no research to explore the imaging standards related to the possibility of natural pregnancy after 4D HyCoSy. If a predictive model of postoperative natural pregnancy was established using the analysis of clinical data combined with imaging characteristics of 4D HyCoSy of patients with tubal factor infertility, clinical decision-making can be wisely guided in the future. This study aims to establish a predictive model of natural pregnancy after 4D HyCoSy based on clinical data and imaging characteristics of patients with tubal factor in fertility. METHODS: A retrospective study was conducted for patients who were diagnosed with tubal factor infertility in Hunan Guangxiu Hospital from February 2017 to May 2018. The patients ought to possess complete 4D HyCoSy imaging data and at least one-side-unobstructed fallopian tube. General clinical data and imaging data were collected. Pregnancy outcome was followed up till 3 months after 4D HyCoSy. According to pregnancy outcome, patients were divided into a pregnancy group and a non-pregnancy group. Binary logistic regression was used to analyze the correlation between various variables and natural pregnancy after 4D HyCoSy. The variables with significant difference (P<0.05) in single-factor logistic regression were included in the natural pregnancy probability prediction model. The classification accuracy was further verified with 10-fold cross-validation. RESULTS: A total of 1 085 patients with clinically suspected tubal factor infertility who met the requirements and followed the doctors' prescription were collected. Clinical characteristics (age and duration of infertility) and 4D HyCoSy imaging characteristics (thickness of endometrium from the 3rd to the 7th day after the end of menstruation, visualization of the left fallopian tube, the diffusion of contrast agent around the left ovary, and the diffusion of contrast agent around the right ovary) were independent predictors for natural pregnancy 3 months after 4D HyCoSy. A natural pregnancy probability prediction model was established with the area under the curve (AUC) verified by the 10-fold cross-validation all greater than 0.75, and the best AUC was 0.868. The Q value obtained by the prediction model was the probability of natural pregnancy, and the cutoff value was 0.5. When the Q value was greater than 0.5, it was recommended to attempt natural pregnancy for 3 months, and when the Q value was less than 0.5, in vitro fertilization was adviced. CONCLUSIONS: A predictive model for the evaluating probability of natural pregnancy in women with tubal factor infertility after 4D HyCoSy is successfully established based on the analysis for clinical data and imaging characteristics. This model shows a great potential in assisting clinical decision making.

Spontaneous rupture of an ovarian artery during pregnancy: A case report and literature review. / å¦Šå¨ æœŸåµå·¢åŠ¨è„‰è‡ªå‘æ€§ç ´è£‚1ä¾‹åŠæ–‡çŒ®å¤ä¹ .

Spontaneous rupture of the ovarian artery is very rare and can cause retroperitoneal hemorrhage, which is seriously life-threatening. Herein, we reported a case of massive retroperitoneal hematoma caused by spontaneous rupture of the right ovarian artery during pregnancy and intrauterine fetal death. A 32-year-old woman, gravida 6 para 5, had non-specific right lower abdomen and low back pain in the third trimester. Emergency cesarean section was performed due to the increased pain and decreased fetal heart rate. A huge retroperitoneal hematoma and intrauterine fetal death were found. Then, the abdomen was closed due to unknown source of bleeding and unstable vital signs. Computed tomography scan was conducted to clarify the extent of the retroperitoneal hematoma. Digital subtraction angiography confirmed the rupture of the right ovarian artery. A transcatheter artery embolization was successfully performed to control the bleeding. The patient ultimately recovered well after surgery.