OBJECTIVE: To depict the cell landscape and molecular biological characteristics of human intrauterine adhesion (IUA) so as to better understand its immune microenvironment and provide new inspirations for clinical treatment. METHODS: Four patients with IUA who underwent hysteroscopic treatment at Dongguan Maternal and Child Health Care Hospital from February 2022 to April 2022 were selected as the study subjects. Hysteroscopy was used to collect the tissues of IUA, which were graded based on the patient's medical history, menstrual history and status of IUA. Library construction, sequencing, single cell data comparison and gene expression matrix construction were carried out in strict accordance with the single cell RNA sequencing process. Thereafter, the UMAP dimension reduction analysis of cell population and genetic analysis were carried out based on the cell types. RESULTS: A total of 27 511 cell transcripts were obtained from four moderately graded IUA tissue samples and assigned to six cell lineages including T cells, mononuclear phagocytes, epithelial cells, fibroblasts, endothelial cells and erythrocytes. Compared with normal uterine tissue cells, the four samples showed different cell distribution, and the proportions of mononuclear phagocytes and T cells in sample IUA0202204 were significantly increased, suggesting a strong cellular immune response. CONCLUSION The cell diversity and heterogeneity of moderate IUA tissues have been described. Each cell subgroup has unique molecular characteristics, which may provide new clues for further study of the pathogenesis of IUA and heterogeneity among the patients.
Pregnancy ; Female ; Child ; Humans ; Endothelial Cells ; Uterine Diseases/complications* ; Hysteroscopy/methods* ; Tissue Adhesions/etiology* ; Sequence Analysis, RNA

OBJECTIVES: Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare female genital tract malformation, and there are few large sample studies reported at home and abroad. The clinical manifestations of this syndrome are diverse, and insufficient understanding may delay the diagnosis and treatment of the patients. This study aims to analyze the clinical characteristics of different types of HWWS patients, and to improve the diagnosis and treatment of HWWS. METHODS: The clinical data of patients with HWWS who were hospitalized in the Department of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University from October 1, 2009 to April 5, 2022 were retrospectively analyzed. The age, medical history, physical examination, imaging examination and treatment of the patients were collected for statistical analysis. The patients were divided into an imperforate oblique vaginal septum type, a perforate oblique vaginal septum type, and an imperforate oblique vaginal septum and cervical fistula type. The clinical characteristics of different types of HWWS patients were compared. RESULTS: A total of 102 HWWS patients were enrolled, with age of 10-46 years old, including 37 (36.27%) patients with type I, 50 (49.02%) type II, and 15 (14.71%) type III. All patients were diagnosed after menarche, with an average age of (20.5±7.4) years. There were significant differences in the age of diagnosis and course of disease among the 3 types of HWWS patients (both P<0.05). Patients with type I had the youngest age of diagnosis [(18.0±6.0) years] and the shortest course of disease (median course of 6 months), while patients with type III had the oldest age of diagnosis [(22.9±9.8) years] and the longest course of disease (median course of 48 months). The main clinical manifestation of type I was dysmenorrhea, and the main clinical manifestation of type II and type III was abnormal vaginal bleeding. Of the 102 patients, 67 (65.69%) patients had double uterus, 33 (32.35%) had septate uterus, and 2 (1.96%) had bicornuate uterus. The vast majority of patients had renal agenesis on the oblique septum, and only 1 patient had renal dysplasia on the oblique septum. The oblique septum located on the left side in 45 (44.12%) patients and on the right side in 57 (55.88%) patients. There were no significant differences in uterine morphology, urinary system malformation, pelvic mass, and oblique septum among the 3 types of HWWS patients (all P>0.05). Six (5.88%) patients had ovarian chocolate cyst, 4 (3.92%) patients had pelvic abscess, and 5 (4.90%) patients had hydrosalpinx. All patients underwent vaginal oblique septum resection. Among them, 42 patients underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen because they had no sexual life history, and the remaining 60 patients underwent traditional oblique vaginal septum resection. Among the 102 patients, 89 patients were followed up for 1 month to 12 years. The symptoms of vaginal oblique septum in 89 patients such as dysmenorrhea, abnormal vaginal bleeding and vaginal discharge were improved after operation. Among the 42 patients who underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen, 25 patients underwent hysteroscopies again 3 months after operation, and there was no obvious scar formation at the oblique septum incision site. CONCLUSIONS Different types of HWWS have different clinical manifestations, but all can be manifested as dysmenorrhea. The patient's uterine morphology can be manifested as double uterus, septate uterus, or bicornuate uterus. The possibility of HWWS should be considered if uterine malformation is combined with renal agenesis. Vaginal oblique septum resection is an effective treatment.
Pregnancy ; Humans ; Female ; Adolescent ; Young Adult ; Adult ; Child ; Middle Aged ; Male ; Dysmenorrhea ; Retrospective Studies ; Kidney Diseases ; Bicornuate Uterus ; Uterine Duplication Anomalies ; Uterine Hemorrhage

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O₂) or hypoxia condition (1%O₂). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×10⁶/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×10⁶/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD₃₁], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD₃₁ showed that, the expressions of VEGFA and CD₃₁ in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD₃₁ in BMSC-exo group and CD₃₁ in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD₃₁ in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.
Rats ; Female ; Humans ; Animals ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism* ; Vascular Endothelial Growth Factor A ; Exosomes/metabolism* ; Uterine Diseases/therapy* ; Collagen ; Hypoxia/therapy* ; Fibrosis ; Mesenchymal Stem Cells/metabolism* ; Oxygen

OBJECTIVE: To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT).METHODS: Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors.RESULTS: A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282–0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189–0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067).CONCLUSION: Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.
Adenocarcinoma ; Cervix Uteri ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Humans ; Hysterectomy ; Lymphatic Diseases ; Neoplasm, Residual ; Recurrence ; Standard of Care ; Uterine Cervical Neoplasms

Uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are very rare tumors that occur mainly in the uterine fundus of women in reproductive age. These tumors can be classified into group 1 and group 2 by histological results. In group 1, epithelial-like differentiation is partially observed in the tumors. In group 2, sex-cord elements are predominant in uterine mural mass. We experienced UTROSCT group 1 in a 29-year-old woman who complained of severe abdominal pain that started one week after delivery and UTROSCT group 2 case in a 49-year-old woman who complained of dysfunctional uterine bleeding. We report two different types of UTROSCT cases that we experienced.
Abdominal Pain ; Adult ; Female ; Humans ; Metrorrhagia ; Middle Aged ; Sex Cord-Gonadal Stromal Tumors ; Uterine Diseases ; Uterine Neoplasms

Placenta accreta is one of the most feared complications among gravid women, as it is associated with massive and potentially life-threatening intrapartum and postpartum hemorrhage. Due to its natural history, placenta accreta is only naturally seen or expected as a cause of bleeding only among obstetric patients. This case report describes a rare manifestation of profuse abnormal uterine bleeding secondary to a placenta accreta in a non-gravid patient. The non-pregnant state was evidenced by the absence of history of amenorrhea and pregnancy signs and symptoms, a negative urine pregnancy test and normal serum bhcg results. A diagnosis of placenta accreta was mainly based on a post-hysterectomy histopathological examination. Theoretical explanations to explain this phenomenon is discussed in this case report.
Pregnancy ; Female ; Placenta Accreta ; Uterine Diseases ; Uterine Hemorrhage

Arteriovenous malformations (AVM) are vascular disorders with a mixture of arterial, venous and small capillary-like channels with fistulous connections. Uterine arteriovenous malformations are rare cause of abnormal uterine bleeding with only a few reported cases. They may arise from pregnancy, miscarriage, previous cesarean section or other uterine surgery and gestational trophoblastic disease. Diagnosis can be made through angiography or doppler ultrasonography. Traditionally, uterine AVMs are treated with hysterectomy but with the advances in technology, minimally invasive conservative approaches such as radiologic arterial embolization or laparoscopic uterine artery ligation have become available. We present a case of a 29-year-old, G2P1 (1011) who had a three- month history of heavy, intermittent vaginal bleeding from uterine arteriovenous malformation after a miscarriage. Laparoscopic bilateral uterine artery occlusion, offered a minimally invasive treatment with high symptomatic effectiveness.
Uterine Artery ; Arteriovenous Malformations ; Uterine Diseases ; Ligation ; Uterine Hemorrhage

OBJECTIVES: To perform a systematic review and meta-analysis of the prognostic value of post-treatment 18F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in uterine cervical cancer patients treated with radiotherapy (RT) with or without chemotherapy. METHODS: PubMed and Embase databases were searched up to July 22, 2018, for studies which evaluated the response outcomes of ¹⁸F-FDG PET following RT, and their prognostic significance in uterine cervical cancer was assessed with overall survival (OS) or progression-free survival (PFS) as endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. RESULTS: Eleven studies with 12 patient cohorts including 1,104 patients were included. For a quantitative synthesis of OS, 7 cohorts were included. Two cohorts which reported disease-specific survival instead of OS were also included with flexibility. Pooled HR of complete metabolic response (CMR) compared to partial metabolic response (PMR) was 0.19 (95% confidence interval [CI]=0.11–0.31). Pooled HR of CMR compared to progressive metabolic disease (PMD) was more evident at 0.07 (95% CI=0.04–0.12), and that of CMR compared to both PMR and PMD was 0.20 (95% CI=0.12–0.34). Quantitative synthesis for PFS was performed with a total of 8 cohorts. Pooled HR of CMR was 0.17 (95% CI=0.10–0.29) compared to PMR, 0.02 (95% CI=0.01–0.06) compared to PMD and 0.12 (95% CI=0.07–0.19) compared to both PMR and PMD. CONCLUSION: Response results of post-RT ¹⁸F-FDG PET were significant prognostic factors in patients with uterine cervical cancer, and ¹⁸F-FDG PET could be a reasonable follow-up imaging modality.
Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Electrons ; Follow-Up Studies ; Humans ; Metabolic Diseases ; Pliability ; Positron-Emission Tomography ; Radiotherapy ; Uterine Cervical Neoplasms

The pathogenesis and therapeutic treatment of intrauterine adhesions (IUAs) remain unsolved, highlighting the need for stable and effective experimental animal models. In this study, uterine electrocoagulation of twenty-one female New Zealand White rabbits was carried out to establish an IUA model. As rabbits have two completely separate uterine horns, each rabbit had its own internal control: one uterine horn was given an electrothermal injury (Group A, n=21), and the contralateral uterine horn received no treatment and served as the control (Group B, n=21). The endometrial morphology, number of endometrial glands, area of endometrial fibrosis, and number of implanted fetuses were compared between the two groups. In Group A, the numbers of endometrial glands on Days 7 and 14 and the number of implanted fetuses were significantly lower than those in Group B (P<0.05, P<0.05, and P<0.01, respectively), while the ratio of the area with endometrial stromal fibrosis to the total endometrial area was significantly increased (P<0.01). These results suggest that this method of electrothermal injury is effective for the establishment of a rabbit IUA model between 7 and 14 d after surgery.
Animals ; Disease Models, Animal ; Electrocoagulation ; Endometrium ; pathology ; Female ; Pregnancy ; Rabbits ; Tissue Adhesions ; etiology ; pathology ; therapy ; Uterine Diseases ; etiology

BACKGROUND: Human papillomavirus (HPV) genotypes that infect the genital tract play a main etiologic role in cervical cancer progression. Other environmental factors, such as sexually transmitted diseases and the host genetic pattern, contribute to infection persistence of the uterus and cervical epithelium in sustaining their malignancy. The Janus kinase 2 is a non-receptor tyrosine kinase in cell signaling process of tumor genesis. In the present study, JAK2 V167F mutation was distinguished in women with sexually transmitted infections, such as Herpes simplex virus 2, Chlamydia trachomatis and Mycoplasma genitalium and cervical cancer. METHODS: This case-control survey was performed on 195 liquid based cytology of women specimens. Fifty, 98, and 47 samples were from women with known cervical cancer, HPV positive and HPV negative, respectively. Single nucleotide polymorphism analysis, sexually transmitted infections detection and HPV genotyping were carried out using approved PCR- RFLP, in-house multiplex TaqMan Real Time PCR and the reverse dot blot hybridization assay. RESULTS: HPVs 6, 16, 18, 11, 31, and 51 were the most common genotypes. The prevalence rate of multiple HPV genotypes was 46.0% to 10.1%. Analysis of JAK2 V617F (1849 G > T) showed that prevalence of mutation was GG (65.1%), GA (34.9%), and TT (0%), respectively. There were no statistically significant differences between this mutation and variables of population survey (P ≥ 0.05). CONCLUSIONS: The molecular epidemiology study on the genetic polymorphisms, i.e., JAK2 V617F and other single nucleotide polymorphisms as a diagnostic tool is necessary for cancer screening and prophylactic programs.
Case-Control Studies ; Chlamydia trachomatis ; Early Detection of Cancer ; Epithelium ; Female ; Genotype ; Herpesvirus 2, Human ; Humans ; Iran ; Janus Kinase 2 ; Molecular Epidemiology ; Mycoplasma genitalium ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Prevalence ; Protein-Tyrosine Kinases ; Real-Time Polymerase Chain Reaction ; Sexually Transmitted Diseases ; Uterine Cervical Neoplasms ; Uterus