We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.

The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.

Triazine herbicides have been widely detected in marine environments because of their extensive usage in agriculture, but their impact on marine organisms is unclear. In this study, marine medaka (Oryzias melastigma) embryos were exposed to 0, 1, 10, 100, and 1000 μg/L prometryn, one of the most detected triazine herbicides, to investigate its potential effects. The results showed that 1, 10, 100, and 1000 µg/L prometryn not only induced yolk sac shrinkage and heart malformations, but also significantly delayed the hatching time and increased the heart rate and hatching failure rate of embryos. Moreover, 1, 10, 100, and 1000 μg/L prometryn caused obvious malformations and decreased the body length of the newly hatched larvae. After 21 d of exposure, increased larval death rate, decreased body length and width, and higher lipid accumulation were observed in the larvae from all prometryn groups. Furthermore, prometryn exposure upregulated the expression levels of cardiac development-related genes GATA, COX, ATPase, SmyD1, EPO, FGF8, NKX2, and BMP4 in the larvae. Transcriptome analysis revealed that 10 μg/L prometryn upregulated 604 genes, and the topmost pathways of differentially expressed genes were the complement and coagulation cascades and AMPK signaling pathways. qPCR results confirmed that prometryn exposure significantly increased the expression levels of the complement and coagulation cascade genes f2, f5, c3, and c5. This study demonstrated that environmentally relevant concentrations of prometryn induced significant toxicity in the early life stages of marine medaka. Therefore, the health risks of herbicides to marine organisms are of great concern.

UNASSIGNED: Recent evidence from a meta-analysis indicates that maternal prenatal exposure, single or repeated, to non-steroidal anti-inflammatory drugs (NSAIDs) or non-opioid painkillers, is associated with increased risk of cerebral palsy and cognitive-behavioral disorders in offspring. One potential route of action is interference with the neurulation process and hence early brain development.
UNASSIGNED: To examine the effect of prenatal exposure to common NSAIDs and non-opioid drugs on neurulation using an in vitro whole embryo culture system.
UNASSIGNED: Mouse embryos from in-bred Institute of Cancer Research albino strain mice were exteriorized on embryonic day 7.5 and cultured for 48 h in either 1 mL heat-inactivated rat serum + 0.1% dimethyl sulfoxide (\"Control\") or 1 mL of rat serum supplemented with six increasing concentrations of laboratory-grade aspirin, paracetamol, and ibuprofen (\"Experimental\"). After culture, embryo morphological and developmental parameters were documented using standardized scoring systems at each dosage concentration. The assessed concentration in rat serum culture ranged from 1.23 to 13.57 mg/mL for aspirin and 0.06-4.93 mg/mL for paracetamol and ibuprofen. The equivalent respective human dosages were 600-6600 mg and 30-2400 mg.
UNASSIGNED: Between-group comparisons (\"Control\" vs \"Experimental\") and post-hoc pair-wise tests, adjusted for multiple comparisons, indicating no statistically significant effect on crown-rump length (p > .21), head length (p > .28), somite number (p > .25), incidence of absent hindlimb buds (p > .18), yolk sac circulation score (p > .07) and posterior neuropore closure (p > .35) in the aspirin, paracetamol and ibuprofen experiments. All embryos had forelimb buds, closed anterior neuropores and none had neural tube defects.
UNASSIGNED: This study has demonstrated that there are no safety concerns regarding high-dose aspirin, ibuprofen, and paracetamol on mice\'s embryonic development.

In the past 5 years, the time-lapse culture system (TLS) has gradually been applied to the field of assisted reproduction. However, there are few reports on the comparison between this system and the conventional culture system (CS) on the outcome of newborns. As a new model in embryo culture, we should pay attention to its neonatal outcomes. We examined 15,252 fresh transfer cycles processed between January 2016 and December 2019. After propensity score matching, embryos in two groups, TLS and CS, had similar rates of miscarriages, ectopic pregnancy, and live delivery (P > 0.05). Embryos in the TLS group achieved higher clinical pregnancy and implantation rates (P < 0.05). Of the perinatal and neonatal outcomes, singletons and twins were analyzed separately. No significant differences were observed in gestational age, preterm deliveries, birth weight, and sex ratio (P > 0.05). Incidences of malformations of babies delivered from CS and TLS groups were also similar between the two groups. Embryos cultured in a TLS are as safe as CS with regard to neonatal outcomes, including congenital malformations.

OBJECTIVE: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.
METHODS: PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.
RESULTS: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50-1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79-1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34-5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51-2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90-1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41-0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.
CONCLUSIONS: LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.
UNASSIGNED: PROSPERO (No CRD 42017069367).

Cyproconazole is a triazole fungicide used to protect a diverse range of fruits, vegetables, and grain crops. As such, it has the potential to enter aquatic environments and affect non-target organisms. The objective of this study was to assess the acute toxicity of the triazole fungicide cyproconazole to zebrafish embryos by assessing mortality, developmental defects, morphological abnormality, oxidative respiration, and locomotor activity following a 96-h exposure. Zebrafish embryos at 6-h post-fertilization (hpf) were exposed to either a solvent control (0.1% DMSO, v/v), or one dose of 10, 25, 50, 100, 250, and 500 μM cyproconazole for 96 h. Data indicated that cyproconazole exhibited low toxicity to zebrafish embryos, with a 96-h LC50 value of 90.6 μM (~ 26.4 mg/L). Zebrafish embryos/larvae displayed a significant decrease in spontaneous movement, hatching rate, and heartbeats/20 s with 50, 100, and 250 μM cyproconazole exposure. Malformations (i.e., pericardial edema, yolk sac edema, tail deformation, and spine deformation) were also detected in zebrafish exposed to ≥ 50 μM cyproconazole, with significant increases in cumulative deformity rate at 48, 72, and 96 hpf. In addition, a 20-30% decrease in basal and oligomycin-induced ATP respiration was observed after 24-h exposure to 500 μM cyproconazole in embryos. To determine if cyproconazole affected locomotor activity, a dark photokinesis assay was conducted in larvae following 7-day exposure to 1, 10, and 25 μM cyproconazole in two independent trials. Activity in the dark period was decreased for zebrafish exposed to 25 μM cyproconazole in the first trial, and hypoactivity was also observed in zebrafish exposed to 1 μM cyproconazole in a second trial, suggesting that cyproconazole can affect locomotor activity. These data improve understanding of the toxicity of cyproconazole in developing zebrafish and contribute to environmental risk assessments for the triazole fungicides on aquatic organisms. We report that, based on the overall endpoints assessed, cyproconazole exhibits low risk for developing fish embryos, as many effects were observed above environmentally-relevant levels.

OBJECTIVE: To analyze the spectrum of type I and type II malformations in Chinese patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a cross-sectional descriptive study that used data from a National Clinical Research Center for Obstetrical and Gynecological Diseases of China, reviewed from January 2009 to July 2017. Data of in- and outpatients with MRKH syndrome were reviewed and analyzed.
RESULTS: A total of 274 cases were included in the analysis: 197/274 (71.9%) with type I MRKH syndrome and the remaining 77/274 (28.1%) with type II MRKH syndrome. The rate of concurrent deformities was 32/244 (13.1%) for renal malformation, and 49/125 (39.2%) for skeletal malformation. Nine patients had renal and skeletal malformations (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia). Cardiac, neurologic, and other malformations (eg, anal atresia) were sporadic. The percentage of type II MRKH syndrome in our cohort was considerably higher than that reported 43/594 (7.2%) in a previous large-scale study in southern China, but lower than that 489/1259 (46.2%) reported for Caucasian individuals.
CONCLUSIONS: The spectrum of type I and type II MRKH syndrome varies across different races and geological locations.

Excessive fluoride in natural water ecosystem has the potential to detrimentally affect amphibians, but little is known of such effects or underlying mechanisms in Bufo gargarizans embryos. In the present study, the effects of fluoride exposure on B. gargarizans embryos were investigated. First, fluoride teratogenic experiment showed that the 9 days EC50 of fluoride on B. gargarizans embryos was 177.62 mg/L. Then, we studied the sublethal effects of fluoride on B. gargarizans embryos at control, 0.7, 4.1, 19.6, 41.9, and 62.7 mg/L fluoride concentration. Malformation, growth, and development of embryos were monitored, and type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were measured. Our results showed the morphological malformations, such as tail curvature (lordosis), edema, cuticularized ciliated cells, and hyperplasia were occurred during fluoride exposure. Growth and development were all inhibited at 19.5, 41.9, and 62.7 mg/L fluoride-treated groups after 9 days\' exposure. According to real-time PCR results, exposure to fluoride upregulated Dio3 and TRβ mRNA expression and downregulated Dio2 and TRα mRNA level. All above indicated that excessive fluoride could induce morphology malformations, inhibit embryonic growth and development, and disrupt the normal function of maternal thyroid hormone in B. gargarizans embryos. Environ. Mol. Mutagen. 59:123-133, 2018. © 2017 Wiley Periodicals, Inc.

OBJECTIVE: To analyze the phenotypic and clinical aspects of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.
METHODS: Cross-sectional study.
METHODS: University hospital.
METHODS: Five hundred and ninety-four patients with MRKH syndrome.
METHODS: Clinical examination, abdominal or perineal/rectal ultrasound, magnetic resonance imaging, hormonal profile, karyotype, and laparoscopy.
METHODS: Clinicopathologic data, VCUAM (vagina cervix uterus adnex-associated malformation) classification, types with cycle phase, and karyotype.
RESULTS: We identified associated malformations in 43 out of 594 (7.2%) cases of MRKH. The 594 patients could be grouped into hormone phases: 53.7% follicular, 35.2% luteal, and 11.1% ovulatory. The major karyotype of MRKH patients was 46,XX; abnormal karyotypes were found in two cases.
CONCLUSIONS: A lower proportion of associated malformations were found when compared with those provided in the current literature. Renal anomalies were the most frequent associated malformations, and most of the patients presented with a normal karyotype. Given the large cohort of this study, the lower malformation rates might be related to geographic or referral patterns, so further investigation is warranted.