Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

A retrospective analysis of the patient journey for children with an unerupted maxillary central incisor.

BACKGROUND: Maxillary central incisors (MCI) are the third most impacted teeth. Timely multidisciplinary management is indicated as unerupted incisors can cause functional- and appearance-related distress. AIM: To assess the patient journey for children with unerupted MCI, including referral, clinical assessment, surgical management and follow-up treatment, and highlight areas for improvement, as well as identify factors impacting orthodontic treatment burden (OTB). DESIGN: A retrospective service evaluation of children aged 6-16 years who had surgical management of unerupted MCI under general anaesthetic (GA) between 2018 and 2021. RESULTS: Fifty-two children with 62 unerupted MCI were identified. Mean age at referral was 8.8 years. Most children (82.7%) had supernumerary teeth in the anterior maxilla. Mean time between listing for GA and surgery increased from 4.3 to 15.2 months following the COVID-19 lockdown. Mean age at surgery was 10.4 years. Supernumerary removal and incisor exposure and bond was the most common treatment (56.6%). Most patients required hospital orthodontic treatment post-surgery (65.4%). CONCLUSION: Most children referred were below 9 years (60.1%); these children had reduced OTB compared to those who had been referred at an older age. Stage of root development was also a significant predictor in OTB. An unexpected finding was that conical supernumeraries were found to prevent MCI eruption.

Translation and validation of the Chinese version of the menstrual distress questionnaire.

BACKGROUND: The Menstrual Distress Questionnaire (MDQ) is a commonly used questionnaire that assesses various symptoms and distress associated with the menstrual cycle in women. However, the questionnaire has not been completely translated into Chinese with rigorous reliability and validity testing. METHODS: This study translated the Menstrual Distress Questionnaire Form Cycle (MDQC) from English into Chinese: MDQCC in two stages. First, it was translated forward and backward using Jones' model; second, to test the validity and reliability, 210 Chinese-speaking women were recruited through online announcements and posters posted between June 2019 and May 2020. Expert validity, construct validity, convergent validity, and factorial validity were determined using content validity index (CVI), intraclass correlation coefficient (ICC), composite reliability (CR), and exploratory factor analysis, respectively. For concurrent criterion validity, MDQCC score was compared with three existing pain scales. Reliability was evaluated using internal consistency across items and two-week test-retest reliability over time. RESULTS: The CVI for content validity was .92. Item-CVI for expert validities among the 46 items ranged from .50 - 1; scale-CVI for the eight subscales, from .87 - 1; ICC, from .650 - .897; and CRs, from .303 - .881. Pearson correlation coefficients between MDQCC and short-form McGill pain questionnaire, present pain intensity, and visual analog scale scores were .640, .519, and .575, respectively. Cronbach's α for internal consistency was satisfactory (.932). ICC for test-retest reliability was .852 for the entire MDQCC. CONCLUSION: MDQCC was valid and reliable for Mandarin Chinese-speaking women. It can be used to evaluate female psychiatric symptoms related to the menstrual cycle in future work.

The Menstrual Distress Questionnaire has been used to evaluate menstrual distress, including dysmenorrhoea and premenstrual syndrome. This questionnaire has been translated into Persian, Korean, Japanese, and Cantonese, rendering it to be used more and more widely all over the world. The study translated all 46 items of the Menstrual Distress Questionnaire from English to Mandarin Chinese using a two-stage strategy. The Chinese version of this questionnaire developed by the present study was found to be a valid and reliable tool in Chinese Mandarin-speaking female populations. It could be used to evaluate women's physical and psychiatric symptoms related to the menstrual cycle in future works.

Associations of Endometriosis and Hormone Therapy With Risk of Hyperlipidemia.

Using claims data from the universal health insurance program of Taiwan, we conducted a retrospective cohort study to investigate whether endometriosis and hormone therapy are associated with the risk of developing hyperlipidemia. We selected 9,155 women aged 20-55 years with endometriosis diagnosed during the period 2000-2013 and 212,641 women without endometriosis with a median follow-up time of 7 years. Among patients with endometriosis, 86% of cases were identified on the basis of diagnosis codes with an ultrasound claim, and 14% were defined by diagnostic laparoscopy or surgical treatments. In a Cox proportional hazards model, the adjusted hazard ratio was 1.30 (95% confidence interval (CI): 1.19, 1.41) for all women, 1.04 (95% CI: 0.81, 1.32) for women under 35 years of age, 1.17 (95% CI: 1.03, 1.32) for women aged 35-44 years, and 1.34 (95% CI: 1.18, 1.52) for women aged 45-54 years. Hysterectomy and/or bilateral oophorectomy accounted for 46.9% of the association between endometriosis and hyperlipidemia, and hormone therapy accounted for 21.6%. Among women with endometriosis, the marginal structural model approach adjusting for time-varying hysterectomy/bilateral oophorectomy showed no association between use of hormone medications and risk of hyperlipidemia. We concluded that women with endometriosis are at increased risk of hyperlipidemia; use of hormone therapy by these women was not independently associated with the development of hyperlipidemia.

Association of pelvic inflammatory disease (PID) with ovarian cancer: a nationwide population-based retrospective cohort study from Taiwan.

BACKGROUND: Pelvic inflammatory disease (PID) is an important health issue for women. Infection and inflammation play an important role in carcinogenesis and PID has been reported to be associated with ovarian cancer in some small scale studies. AIM: We sought to determine whether PID is associated with an elevated risk of ovarian cancer in Asian women. METHODS: Using data from Taiwan's National Health Insurance Research Database (NHIRD), our retrospective cohort study included women diagnosed with PID (cases) between the years of 2000 till 2012. Each case was matched with two women without PID (controls) by age and the year of first entry into the database. Both study cohorts were followed-up until the first event of ovarian cancer, withdrawal from the NHI program, death, or the end of the study period (December 31, 2012). Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs and aHRs) with their corresponding 95% confidence intervals (95% CIs) for the association of PID and ovarian cancer risk, with and without adjusting for potential confounders. RESULTS: During an approximate 10 years of follow-up, cases were significantly more likely than controls to develop ovarian cancer (incidence rates of 0.27 and 0.16 per 1,000 person-years, respectively; P < 0.001). Women with a history of PID had a 1.49-fold elevated risk for ovarian cancer (aHR, 1.49; 95% CI, 1.21-1.84; P < 0.001). CONCLUSION: Our study evidence supports the contention that PID increases the risk of developing ovarian cancer among Taiwanese women. Gynecologists should undertake careful assessments and closely follow patients with PID, who are at long-term risk of developing ovarian cancer. Our findings need further verification in other international cohorts.

Association between hypertensive pregnancy disorders and future risk of stroke in Taiwan: a Nationwide population-based retrospective case-control study.

BACKGROUND: The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. METHODS: Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. RESULTS: During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817-2.505; P < 0.001). CONCLUSION: Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P < 0.001) higher risk of developing stroke in the future.

Major depressive episodes during pregnancy and after childbirth: A prospective longitudinal study in Taiwan.

BACKGROUND: Major depressive episodes (MDEs) are common during pregnancy and postpartum periods, and the consequences can be severe to mother and offspring. Few studies have investigated the clinical factors associated with the onset and remission of perinatal depression in different time points. METHODS: A cohort of 234 pregnant women was recruited and assessed with structured Mini-International Neuropsychiatric Interview (MINI) for diagnoses of MDEs. The severity of mood status was measured with Taiwanese version of the Edinburgh Postnatal Depression Scale (EPDS-T) and the second edition of Beck Depression Inventory (BDI-II) at 16 weeks' gestation, 28 weeks' gestation and 4 weeks postpartum. Statistical analysis was conducted by independent t-tests, chi-squared, and Fisher's exact tests. RESULTS: Thirty-one pregnant women (13.2%) developed MDEs; 11 (4.7%) at the 16th week, 8 (3.4%) at the 28th week of gestation, and 12 (5.1%) at the 4th week of postpartum. Among the 19 women with prenatal MDEs, 9 (47%) experienced remission by the end of pregnancy, and 10 sustained, resulting in the cumulative prevalence of 9.4% (22 out of 234) for postpartum MDEs. Women with lower levels of education, family history of psychiatric disorders, lack of postpartum recuperation, and family-bond stress were more likely to experience MDEs. More preterm birth and lower birth weights were reported in postpartum-onset than pregnancy-onset MDEs. Psychiatric interventions were associated with a higher percentage of remission of MDE during the perinatal period. CONCLUSION: The findings of this study provide clinical implications for early detection and intervention of MDEs throughout the pregnancy.

Transfusions of least-incompatible blood with intravenous immunoglobulin plus steroids cover in two patients with rare antibody.

BACKGROUND: The therapeutic value of the use of intravenous immunoglobulin (IVIG) to correct anemia and thrombocytopenia as a result of immunologic causes (hemolytic disease of the fetus and newborn and fetal or neonatal alloimmune thrombocytopenia) have been well established. Few published papers exist regarding the use of IVIG in adult settings. We report two patients with clinically significant antibodies against high-incidence antigens, who were successfully transfused with incompatible red blood cells (RBCs), in conjunction with IVIG plus steroids and IVIG. CASE REPORTS: Case 1 was a 25-year-old patient (Hb SC) who was admitted with low hemoglobin (Hb) and low reticulocyte count. A diagnosis of parvovirus-induced RBC hypoplasia was made. The patient's sample contained anti-E, anti-N, and anti-U. The Hb decreased to 37 g/dL and urgent transfusion was provided with E-, N-, "least-incompatible" RBC units covered by IVIG and hydrocortisone. Case 2 was a 54-year-old patient who was admitted after a road traffic accident. Nonspecific weak antibody was detected. She received 6 units of least-incompatible RBCs. She was transferred to another hospital and received 2 least-incompatible units. Hb level decreased further and an additional unit was transfused. Samples were referred to the reference laboratory and strong anti-Jra detected. As there was clinical and laboratory evidence of hemolysis and Jr(a-) units were not available, IVIG was prescribed and least-incompatible units were transfused. RESULTS: There were no hemolytic transfusion reactions, hemolysis ceased, and anemia improved in both cases. CONCLUSION: Prophylaxis with IVIG plus steroids and IVIG should be considered as a therapeutic option when transfusion of incompatible units is necessary.

Genetic variations of MUC17 are associated with endometriosis development and related infertility.

BACKGROUND: Genetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features. METHODS: The study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms. RESULTS: Genotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95% CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype. CONCLUSIONS: MUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population.

Sex Differences in Temporal Trends and Risk Factors of Aortic Dissection in Taiwan.

Background Although sex differences in the epidemiological features of aortic dissection (AD) are known, whether there were sex differences in the associations of comorbidities and risk factors with AD is unclear. We evaluated the temporal trends and risk factors of AD by sex. Methods and Results Using claims data from a universal health insurance program linked to the National Death Registry in Taiwan, we identified 16 368 men and 7052 women with newly diagnosed AD from 2005 to 2018. In the case-control analysis, a matched control group without AD was selected for men and women separately. Conditional logistic regression was used to evaluate risk factors of AD and sex differences. Over the 14 years, the annual incidence of diagnosed AD was 12.69 and 5.34 per 100 000 in men and women, respectively. The 30-day mortality was greater in women than in men (18.1% versus 14.1%; adjusted odds ratio [95% CI], 1.19 [1.10-1.29]), and the sex difference was observed mainly in patients not treated with surgery. The 30-day mortality declined over time in male patients undergoing surgical treatments, but no significantly temporal change was found in other patient groups stratified by sex and surgery. After multivariable adjustments, atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery were associated with a greater increase in the odds of AD occurrence in women than in men. Conclusions Greater 30-day mortality and stronger associations of atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery with AD in women than in men require further attention.

A Novel Cephalometric Approach Aiming to Quantify a Normal Range of Bony Chin Protrusion.

Introduction: Cephalometric analysis is an essential tool in the diagnostics and planning of orthognathic surgery. No objective criterion exists to facilitate decision making regarding genioplasties. Differing opinions amongst clinicians therefore leads to wide variability amongst treatment options offered to potentially suitable patients. This study has three aims. The first was to quantify the distribution of chin morphology amongst the average population using cephalometric analysis. Secondly, we sought to determine whether cephalometric parameters could be used to predict overlying soft tissue changes. Lastly, we consider the use of a new cephalometric angle, BNPg, for pre- and post-operative assessment of genioplasty patients. Methods: This study retrospectively analysed 231 lateral cephalograms. The angle between the landmarks: B point, Nasion and Pogonion was measured to generate 'BNPg' a novel unit to quantify bony chin protrusion. Results: The mean BNPg from all 231 samples was 1.12 degrees with a standard deviation of ± 1.35. Comparison between sexes showed no significant differences between male and females (P = 0.108). Furthermore, bony chin protrusion was found to strongly positively correlate with soft tissue chin appearance (r = 0.731), however, BNPg was found not to correlate with skeletal malocclusion (ANB, r = 0.085). Conclusion: The novel unit BNPg may serve as a useful tool in contributing to the determination of treatment thresholds in osseous genioplasty for desirable aesthetic outcomes and may be used post-operatively to assess outcomes also. As this is a pilot study, further clinical studies would be required to validate this parameter in genioplasty patients, both pre- and post-operatively. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01784-5.

Reliability and validity of the supine-to-stand test in people with stroke.

OBJECTIVE: To investigate the psychometric properties of the supine-to-stand test in people with stroke. DESIGN: Cross-sectional design. SUBJECTS: Fifty-two people with stroke (mean (standard deviation) age 63.13 (6.09) years; time post-stroke 93.13 (61.36) months) and 49 healthy older adults (61.90 (7.29) months). METHODS: Subjects with stroke were recruited from the community dwelling in Hong Kong and  assessed with the supineto- stand test, Fugl-Meyer Motor Assessment, ankle muscle strength test, Berg Balance Scale, limit of stability test, Timed Up-and-Go Test, Six-Minute Walk Test, Chinese version of Activities-specific Balance Confidence scale, Community Integration Measure (CIM-C), and 12-item Short-Form Health Survey (SF-12) in a university-based rehabilitation laboratory. RESULTS: The supine-to-stand test completion time demonstrated excellent intra-rater, inter-rater and test-retest reliability (intraclass correlation coefficient 0.946-1.000) for the people with stroke. The completion time was significantly negatively correlated with Berg Balance Scale, Six-Minute Walk Test, limit of stability - maximal excursion, and limit of stability - endpoint excursion results (r = -0.391 to -0.507), whereas it was positively correlated with the Timed Up-and-Go test results (r = 0.461). The optimal cut-off supine-to-stand test completion time of 5.25 s is feasible for a clinical measure to distinguish the performance of people with stroke from healthy older adults (area under the curve = 0.852, sensitivity = 81.1%, specificity = 84.0%). CONCLUSION: The supine-to-stand test is a reliable, sensitive, specific and easy-to-administer clinical test for assessing the supine-to-stand ability of people with stroke.

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study.

BACKGROUND: Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (MUC2) with the risk of endometriosis and endometriosis-related infertility. METHODS: This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within MUC2 gene were performed by using Taqman genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by χ² test. RESULTS: Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (P = 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (P = 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in MUC2 also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility. CONCLUSIONS: MUC2 polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.

Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia.

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17)(q22;q21) involving the PML and RARA genes is associated with exposure to agents targeting topoisomerase II (topoII), particularly mitoxantrone and epirubicin. We previously have shown that mitoxantrone preferentially induces topoII-mediated DNA damage in a "hotspot region" within PML intron 6. To investigate mechanisms underlying epirubicin-associated t-APL, t(15;17) genomic breakpoints were characterized in 6 cases with prior breast cancer. Significant breakpoint clustering was observed in PML and RARA loci (P = .009 and P = .017, respectively), with PML breakpoints lying outside the mitoxantrone-associated hotspot region. Recurrent breakpoints identified in the PML and RARA loci in epirubicin-related t-APL were shown to be preferential sites of topoII-induced DNA damage, enhanced by epirubicin. Although site preferences for DNA damage differed between mitoxantrone and epirubicin, the observation that particular regions of the PML and RARA loci are susceptible to these agents may underlie their respective propensities to induce t-APL.

A pilot study of microsatellite instability and endometrial cancer survival in white and African American women.

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States and can be classified on the basis of various pathologic, molecular, and genetic features, including microsatellite instability (MSI). As MSI is generally associated with a more favorable outcome in colorectal cancers, it is feasible that microsatellite instability may also influence endometrial cancer survival. We examined MSI and survival in 45 African American and 31 white women diagnosed with endometrial cancer at a large, urban cancer center. Fifty-five tumors were classified as type I and 21 tumors were classified as type II. Unconditional logistic regression models found that microsatellite stable tumors were more frequently observed in white women compared with African American women (odds ratio, 8.61; 95% confidence interval, 1.01-73.69). Type I tumors with MSI were not found to be significantly associated with smoking status, tumor stage, or age. Only one type II tumor was classified as MSI. Neither race nor MSI status was a predictor of death from all causes or only endometrial cancer-related deaths were considered in univariate and multivariate survival models. The potential significance of a larger proportion of MSI tumors found in African American women with type I endometrial cancer should be assessed in a larger prospective study.

Cervical pregnancy: a case report of hysteroscopic resection and balloon compression combined with systematic methotrexate treatment.

OBJECTIVE: Cervical pregnancy is a rare type of ectopic pregnancy. When the pregnancy is terminated, it will sometimes lead to persistent bleeding. In some cases, hysterectomy is inevitable and the patient loses fertility. Therefore, early diagnosis and targeted management with systemic or local injection of methotrexate is the first-line treatment. Multiple interventions of cervical pregnancy were used to prevent massive hemorrhage, including dilatation and curettage, laparoscopic resection, hysteroscopic resection combined with uterine artery embolization, or uterine artery clip. CASE REPORT: We report a case of cervical pregnancy with a high beta-hCG level accompanied by a visible fetal heartbeat that was successfully treated with hysteroscopic cervical tissue resection and balloon compression combined with systemic administration of methotrexate. CONCLUSION: Efficacy and safety with preserved fertility were important issues in the management of cervical pregnancy. We provide a safe, simple and effective treatment of cervical pregnancy.

Genetic variations in UCA1, a lncRNA functioning as a miRNA sponge, determine endometriosis development and the potential associated infertility via regulating lipogenesis.

Endometriosis is a hormone-associated disease which has been considered as the precursor for certain types of ovarian cancer. In recent years, emerging evidence demonstrated potent roles of lncRNA in regulating cancer development. Since endometriosis shares several features with cancer, we investigated the possible involvement of cancer-related lncRNAs in endometriosis, including UCA1, GAS5 and PTENP1. By using massARRAY system, we investigated certain genetic variations in cancer-related lncRNAs that can change the thermo-stability, leading to up-regulation or down-regulation of those lncRNAs. Our data indicated three risk genetic haplotypes in UCA1 which can stabilize the RNA structure and increase the susceptibility of endometriosis. Of note, such alterations were found to be associated with long-term pain and infertility in patients. It has been known that UCA1 can function as a ceRNA to sponge and inhibit miRNAs, resulting in loss-of-control on downstream target genes. Gene network analyses revealed fatty acid metabolism and mitochondria beta-oxidation as the major pathways associated with altered UCA1 expression in endometriosis patients. Our study thus provides evidence to highlight functional/epigenetic roles of UCA1 in endometriosis development via regulating fatty acid metabolism in women.

New Efficient Method for Hysteroscopic Isthmoplasty: Four Simple Steps Lead to a Significant Improvement in Bleeding Status.

We demonstrate an effective reduction in postmenstrual spotting after our novel hysteroscopic isthmoplasty. This study included 66 patients with isthmocele-related postmenstrual spotting confirmed by sonography and diagnostic hysteroscopy between 2000 and 2017. Our new interventions included the following four steps: (1) make a resection gradient of the distal edge of the isthmocele from the ape of the isthmocele down to the cervical outer orifice; (2) resect the distal and proximal niches of the isthmocele; (3) electrocauterize the distal and proximal sides (not only the niche bottom) of the small cave on the scar side of the isthmocele; (4) manage the isthmocele until it is largely connected to the cavity. In our results, all patients underwent extensive hysteroscopic repair of newly hysteroscopic isthmoplasty without any intra- or postoperative complications. After final hysteroscopic repair modification, prolonged menstrual spotting was significantly decreased in 98.2% (53/54) of the patients, and the total number of bleeding days per menstrual cycle significantly decreased from a mean of 15.38 ± 3.3 days to 6.4 ± 1.9 days postoperatively (p < 0.001). Our four-step hysteroscopic technique successfully resolved prolonged menstrual spotting in over 90% of the patients, exceeding the resolution rates of 60−85% achieved with other hysteroscopic techniques used to treat symptomatic isthmocele. No patients experience recurrence after long-term follow up. Four simple steps led to a significant improvement in bleeding status.

A More Diverse Cervical Microbiome Associates with Better Clinical Outcomes in Patients with Endometriosis: A Pilot Study.

Infection-induced chronic inflammation is common in patients with endometriosis. Although microbial communities in the reproductive tracts of patients have been reported, little was known about their dynamic profiles during disease progression and complication development. Microbial communities in cervical mucus were collected by cervical swabs from 10 healthy women and 23 patients, and analyzed by 16S rRNA amplicon sequencing. The abundance, ecological relationships and functional networks of microbiota were characterized according to their prevalence, clinical stages, and clinical features including deeply infiltrating endometriosis (DIE), CA125, pain score and infertility. Cervical microbiome can be altered during endometriosis development and progression with a tendency of increased Firmicutes and decreased Actinobacteria and Bacteroidetes. Distinct from vaginal microbiome, upregulation of Lactobacillus, in combination with increased Streptococcus and decreased Dialister, was frequently associated with advanced endometriosis stages, DIE, higher CA125 levels, severe pain, and infertility. Significantly, reduced richness and diversity of cervical microbiome were detected in patients with more severe clinical symptoms. Clinical treatments against infertility can partially reverse the ecological balance of microbes through remodeling nutrition metabolism and transport and cell-cell/cell-matrix interaction. This study provides a new understanding on endometriosis development and a more diverse cervical microbiome may be beneficial for patients to have better clinical outcomes.

Ribosome Biogenesis Serves as a Therapeutic Target for Treating Endometriosis and the Associated Complications.

Ribosome biogenesis is a cellular process critical for protein homeostasis during cell growth and multiplication. Our previous study confirmed up-regulation of ribosome biogenesis during endometriosis progression and malignant transition, thus anti-ribosome biogenesis may be effective for treating endometriosis and the associated complications. A mouse model with human endometriosis features was established and treated with three different drugs that can block ribosome biogenesis, including inhibitors against mTOR/PI3K (GSK2126458) and RNA polymerase I (CX5461 and BMH21). The average lesion numbers and disease frequencies were significantly reduced in treated mice as compared to controls treated with vehicle. Flow cytometry analyses confirmed the reduction of small peritoneal macrophage and neutrophil populations with increased large versus small macrophage ratios, suggesting inflammation suppression by drug treatments. Lesions in treated mice also showed lower nerve fiber density which can support the finding of pain-relief by behavioral studies. Our study therefore suggested ribosome biogenesis as a potential therapeutic target for treating endometriosis.