WTAP gene variants and susceptibility to ovarian endometriosis in a Chinese population.

Background: Endometriosis is a common chronic gynecologic disorder with a significant negative impact on women's health. Wilms tumor 1-associated protein (WTAP) is a vital component of the RNA methyltransferase complex for N6-methyladenosine modification and plays a critical role in various human diseases. However, whether single nucleotide polymorphisms (SNPs) of the WTAP gene predispose to endometriosis risk remains to be investigated. Methods: We genotyped three WTAP polymorphisms in 473 ovarian endometriosis patients and 459 control participants using the Agena Bioscience MassArray iPLEX platform. The logistic regression models were utilized to assess the associations between WTAP SNPs and the risk of ovarian endometriosis. Results: In the single-locus analyses, we found that the rs1853259 G variant genotypes significantly increased, while the rs7766006 T variant genotypes significantly decreased the association with ovarian endometriosis risk. Combined analysis indicated that individuals with two unfavorable genotypes showed significantly higher ovarian endometriosis risk (adjusted OR = 1.71 [1.23-2.37], p = 0.001) than those with zero risk genotypes. In the stratified analysis, the risk effect of the rs1853259 AG/GG and rs7766006 GG genotypes was evident in subgroups of age ≤30, gravidity≤1, parity≤1, rASRM stage I, and the rs7766006 GG genotype was associated with worse risk (adjusted OR = 1.64 [1.08-2.48], p = 0.021) in the patients with rASRM stage II + III + IV. The haplotype analysis indicated that individuals with GGG haplotypes had a higher risk of ovarian endometriosis than wild-type AGG haplotype carriers. Moreover, false positive report probability and Bayesian false discovery probability analysis validated the reliability of the significant results. The quantitative expression trait loci analysis revealed that rs1853259 and rs7766006 were correlated with the expression levels of WTAP. Conclusion: Our findings demonstrated that WTAP polymorphisms were associated with susceptibility to ovarian endometriosis among Chinese women.

Epidemiologic characteristics and a prognostic nomogram for patients with vulvar cancer: results from the Surveillance, Epidemiology, and End Results (SEER) program in the United States, 1975 to 2016.

OBJECTIVE: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. METHODS: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). RESULTS: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. CONCLUSIONS: The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

Association between ABO blood type and type I endometrial cancer: a retrospective study.

This study aimed to assess the association between ABO blood type and incident of type I endometrial cancer (EC), as well as the stage and differentiation. 213 patients with type I EC and 300 healthy controls were included. As a result, the frequencies of A, B, O, and AB blood types among patients with type I EC were 51 (23.9%), 59 (27.7%), 93 (43.7%) and 10 (4.7%), respectively. There were no significant differences in age, body mass index, and other baseline covariates between groups of ABO blood types (p > .05). Logistic regression model showed that women with blood type O was more likely to develop type I EC than those with type A (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.05-2.63). However, there was no significant association of ABO blood type with stage and differentiation of type I EC (p > .05). In conclusion, blood type O was the most prevalent ABO blood type among patients with type I EC and was associated with increased risk of type I EC, while ABO blood type was not significantly associated with stage or differentiation of type I EC.IMPACT STATEMENTWhat is already known on this subject? Previous studies have produced inconsistent findings on association of ABO blood type with EC. Those studies also did not explore the relationship between ABO blood type and stage or differentiation of type I EC.What the results of this study add? The present study showed that women with blood type O was more likely to develop type I EC than those with type A and there was no significant association of ABO blood type with stage or differentiation of type I EC.What the implications are of these findings for clinical practice and/or further research? Gynaecologists should pay more attention to women with blood type O, who should undergo more active EC screening.

TARDBP promotes ovarian cancer progression by altering vascular endothelial growth factor splicing.

Disruptions in alternative splicing regulation play an essential role in ovarian cancer progression. However, the underlying mechanism remains unclear. TAR DNA-binding protein (TARDBP) plays a crucial role in alternative splicing regulation. Herein we found that TARDBP expression was significantly upregulated in OC tissue samples, particularly in cases of metastasis; further, TARDBP expression was markedly upregulated in OC patients with poor prognosis. These findings were validated by extensive tissue microarray data. TARDBP was also found to promote tumorigenesis and metastasis of OC cells in vitro and in vivo. Mechanistically, TARDBP increased the binding of the splicing factor serine/arginine-rich splicing factor 1 (SRSF1) to intron 7 of vascular endothelial growth factor (VEGF), increasing the formation of the proangiogenic VEGF165 isoform and decreasing that of the antiangiogenic VEGF165b isoform. The abnormal alternative splicing event was responsible for the activation of angiogenesis and contributed to the progression of OC. To conclude, TARDBP was found to regulate the alternative splicing of VEGF via SRSF1, induce the formation of VEGF165 but inhibit that of VEGF165b, and promote OC angiogenesis. Hence, TARDBP can serve as an independent prognostic factor and new target for OC cancer therapy.

Exploring the Association Between Cervical Microbiota and HR-HPV Infection Based on 16S rRNA Gene and Metagenomic Sequencing.

The relationship between the cervico-vaginal microbiome and high-risk human papillomavirus (HR-HPV) is well observed. However, there is a lack of adequate research regarding the cervical microbiota in HR-HPV infection. Most published research results have used 16S rRNA gene sequencing technology; this technology only focuses on marker sequences, resulting in incomplete gene information acquisition. Metagenomic sequencing technology can effectively compensate for the deficiency of 16S rRNA gene sequencing, thus improving the analysis of microbiota function. Cervical swab samples from 20 females with HR-HPV infection and 20 uninfected (Control) women were analyzed through 16S rRNA gene and metagenomic sequencing. Our results indicated that the composition and function of the cervical microbiota of HR-HPV infection differed notably from that of control women. Compared with control women, Firmicutes was decreased during HR-HPV infection, whereas Actinobacteria was increased. At the genus level, Lactobacillus was enriched in control women, while levels of Gardnerella and Bifidobacterium were lower. At the species level, Lactobacillus crispatus, L. jensenii, and L. helveticus were enriched in control women; these were the top three species with biomarker significance between the two groups. Eight pathways and four KEGG orthologies of the cervical microbiota of statistical differences were identified between the HR-HPV infection and control women. Collectively, our study described the cervical microbiota and its potential function during HR-HPV infection. Biomarkers of cervical microbiota and the changed bacterial metabolic pathways and metabolites can help clarify the pathogenic mechanism of HR-HPV infection, making them promising targets for clinical treatment and intervention for HR-HPV infection and cervical carcinoma.

Outcomes of reproduction following cesarean scar pregnancy treatment: A systematic review and meta-analysis.

OBJECTIVES: To explore the reproductive outcomes of women with a history of cesarean scar pregnancy (CSP) and the influence of various treatments on subsequent pregnancy outcomes. STUDY DESIGN: The PubMed, Embase, Medline, Cochrane Library and ClinicalTrial.gov databases were searched for studies with the outcomes of pregnancy after CSP treatment. Studies that reported reproductive outcomes after CSP with more than 5 followed cases were included. The main data collected includes the treatment methods of CSP and subsequent pregnancy outcomes. The main information includes intrauterine pregnancy, recurrent CSP (RCSP), and spontaneous miscarriage, while the secondary information includes complications during pregnancies and the outcomes of childbirths. According to different treatments (conservative treatment, surgical treatment without resection of cesarean scar, and surgical treatment with resection of cesarean scar), a stratified analysis was carried out to compare the influence of treatments on subsequent pregnancy outcomes. RESULTS: A total of 32 studies including 3380 cases of CSP met the inclusion criteria, of which 583 cases conceived again after treatment (including 292 cases of unexpected pregnancy), and finally 178 cases delivered successfully. The follow-up time ranged from 3 to 72 months. Among women with fertility requirements, a total of 291 cases in 403 women were successfully conceived during the follow-up period in 15 studies. Thence the pregnancy rate of women with fertility requirements was 76.2 %. Among all of the 583 successfully conceived women, 83.4 % of them had intrauterine pregnancy, while 15.3 % of cases were RCSP. The total ectopic pregnancy rate reached 16.6 %, covering RCSP and other sites of ectopic pregnancy. 14.6 % of intrauterine pregnancy experienced spontaneous miscarriage. The intrauterine pregnancy rates of the conservative treatment group, the surgical treatment without resection of cesarean scar group, and the surgical treatment with resection of cesarean scar group were 93.1 %, 80.1 % and 86.0 % respectively; the corresponding RCSP rates were 6.9 %, 15.6 % and 14.0 % respectively; and the corresponding spontaneous miscarriage rates were 20.7 %, 13.9 % and 22.2 % respectively. CONCLUSION: The outcomes of reproduction after CSP included intrauterine pregnancy, RCSP and other sites of ectopic pregnancy. Women with a history of CSP still have a high pregnancy rate, but the risk of RCSP and spontaneous miscarriage is also increased. It is impossible to clarify the effect of different treatments on subsequent pregnancy. Whether the resection and repair of cesarean scar can ameliorate reproductive outcomes needs to be further assessed. Further large-scale prospective studies, even RCTs with long-term follow-up are needed to expound the outcomes of reproduction after CSP and the effect of different treatments on subsequent reproductive outcomes.

Retroperitoneal ectopic pregnancy: A literature review of reported cases.

To provide reference for the diagnosis and treatment of retroperitoneal ectopic pregnancy (REP), we conducted a review on all of the reported cases in English by summarizing their clinical manifestation, diagnosis, management and prognosis. A total of 25 literatures including 26 REP cases were collected from PubMed database. 40 % (10/25) of the patients had a history of tubal pregnancy, 65.4 % (17/26) was spontaneous pregnancy, and the average period of amenorrhea was 56.7 days. Abdominal pain is the most common (53.8 %, 14/26) symptom of REP. Ultrasound is the main method of diagnosing REP. Only 30.8 % (8/26) were diagnosed as REP at the initial visit, and 55.6 % (10/18) of those who were misdiagnosed received unnecessary invasive treatment. The pregnancy sites of REP are complex, and it can be simply divided into pelvic REP and abdominal REP. Due to preoperative misdiagnosis, 46.2 % (9/26) of REP experienced two or more treatments. Except for 2 patients who received local methotrexate (MTX) injection in the gestational sac, the other 24 patients underwent surgical treatment, and all patients had a good prognosis. Due to insufficient knowledge, the rate of misdiagnosis and mistreatment of REP is high. The key to diagnosing REP is to consider the possibility of REP and the scanning field during examination can cover the site of pregnancy. Local MTX injection and surgical resection are both effective methods for the treatment of REP.

Single-dose versus multidose metronidazole for the treatment of vaginal trichomoniasis: A meta-analysis.

OBJECTIVE: The purpose of this meta-analysis is to further explore the effectiveness of multidose metronidazole (MTZ) and single-dose MTZ in the treatment of trichomoniasis. STUDY DESIGN: Search all the literature on MTZ for trichomoniasis in the Pubmed, Ovid Embase, Ovid MEDLIN and Cochrane Library databases. The search period is from the establishment of the database to September 10, 2020. Two authors independently screened the literatures based on inclusion and exclusion criteria, and independent extraction and integration of literature data. The main observation indicators were treatment failure rate and side-effects. Data analysis was performed using RevMan5.2 software. The risk ratio (RR) and 95 % confidence interval (CI) were used as the effect scale indicators of the counting data. P < 0.05 was considered to be statistically significant. RESULTS: A total of 2114 articles were retrieved. After screening, a total of 7 articles were included, including 5 randomized controlled trial (RCT) studies and 2 case-control studies. 745 cases were treated with single-dose MTZ, and 732 cases were treated with multidose MTZ. The single-dose MTZ had a higher failure rate for trichomoniasis than the multidose MTZ, and the difference was statistically significant (RR = 1.07, 95 %CI, 1.03-1.11, P = 0.0003). When a HIV-positive study was excluded, the failure rate of the single-dose MTZ was still significantly higher than that of the multidose MTZ (RR = 1.62, 95 %CI, 1.19-2.22, P = 0.002). The side-effects of the single-dose MTZ were higher than those of the multidose MTZ, but the difference was not statistically significant (RR = 1.06, 95 %CI, 0.88-1.27, P = 0.53). CONCLUSION: Although based on available data, multidose MTZ is more effective than single-dose MTZ for trichomoniasis, this advantage is not as obvious as previously proven. This small advantage may be lower if considering the compliance of multidose MTZ in the real world. Therefore, more high-quality studies are needed to confirm this before suggesting a multidose MTZ as the first line treatment for HIV-negative trichomoniasis.

Ectopic pregnancy following in vitro fertilization after bilateral salpingectomy: A review of the literature.

Ectopic pregnancy after bilateral salpingectomy is rare and is therefore easily misdiagnosed. To provide information regarding the clinical manifestations, diagnosis, management, mechanism and prognosis of this condition, we reviewed all cases reported in the English literature. All English language reports on ectopic pregnancy after bilateral salpingectomy were retrieved from the PubMed database. A total of 19 English language articles were collected and 20 cases of ectopic pregnancy were reported. Eleven of the 19 patients had a history of tubal pregnancy on one or both sides. All of these pregnancies were by IVF-ET. The site of ectopic pregnancy was the tubal stump in 8 cases, the abdominal cavity in 4 cases, the ovary in 3 cases, the retroperitoneum in 3 cases, and the uterine cornua in 2 cases. All patients underwent successful resection of the ectopic pregnancy, of which 10 were laparoscopic surgery and 10 were laparotomy. Six of 8 cases of heterotopic pregnancy were successful gestation to the last trimester and were delivered after treatment. Ectopic pregnancy is still possible following IVF-ET after bilateral salpingectomy. The location of these ectopic pregnancies is complex and it is necessary to beware of the possibility of a heterotopic pregnancy.

Transvaginal hysterotomy: A novel approach for the treatment of cesarean scar pregnancy.

The objective of this study was to determine the outcome of using transvaginal hysterotomy as the first-line treatment of cesarean scar pregnancy (CSP). A literature review was performed on all eligible reports using this modality as the first-line treatment of CSP in English report. Relevant publications were obtained from the PubMed electronic database from inception to October 2018. Two hundred and fifteen cases reported in 7 articles were reviewed. The success rate of treatment was 99.5% (214/215), complication rate was 1.4% (3/215), and hysterectomy rate was 0.5% (1/215). Transvaginal hysterotomy could be considered as a good first-line treatment modality for CSP.