FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study.

BACKGROUND: Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. METHODS: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. RESULTS: The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6-88.3) and 5-year overall survival 88.9% (95% CI, 85.5-92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8-86.4] vs. 88.9%, [95% CI, 84.1-93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2-87.4] vs. 87.1%, [95% CI, 83.4-90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6-96.1] vs. 83.0% [95% CI, 77.5-88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2-14.5], p < .001). CONCLUSIONS: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.

Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

Mycobacterium abscessus pulmonary disease presenting with spontaneous pneumomediastinum and subcutaneous emphysema in childhood acute lymphoblastic leukemia: a case report and literature review.

INTRODUCTION: Mycobacterium abscessus is a rapidly growing mycobacterium commonly identified in adults with underlying pulmonary diseases but is rarely observed in children. A better understanding of this pathogen in children is essential. CASE PRESENTATION: We report the case of a 49-month-old female child without previous underlying pulmonary diseases but with acute lymphoblastic leukemia (ALL). The patient was complicated with pneumonia during chemotherapy, which was primarily characterized by spontaneous pneumomediastinum and subcutaneous emphysema on chest computed tomography (CT). M. abscessus sequences were detected by metagenomic next-generation sequencing in bronchoalveolar lavage fluid. With mechanical ventilation, closed thoracic drainage, and anti-infective therapy for 6 months, the patient's infection was controlled. The patient completed 2.5 years of treatment for ALL, and the drugs were discontinued. The patient currently remains in complete hematologic remission. DISCUSSION: We reviewed the literature on 33 children with M. abscessus pulmonary disease. These children mostly had underlying immunodeficiency. Chest CT most often showed nodular shadows, consolidation, and bronchiectasis. Spontaneous pneumomediastinum and subcutaneous emphysema were not reported as major manifestations. CONCLUSION: Spontaneous pneumomediastinum and subcutaneous emphysema were our patient's main characteristics on chest CT, and this study enriches the knowledge regarding possible imaging changes in M. abscessus pulmonary disease in children. This case report reflects good clinical experience in maintaining the balance between chemotherapy and anti-infective therapy in childhood ALL.

Extended vincristine and dexamethasone pulse therapy may not be necessary for children with TCF3-PBX1 positive acute lymphoblastic leukaemia.

The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3-PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non-inferiority analysis of 263 newly diagnosed TCF3-PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG-ALL-2015 clinical trial from January 2015 to December 2019 (ChiCTR-IPR-14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow-up of 4.2 years, the 5-year event-free survival (EFS) and 5-year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1-95.4) and 94.7% (95% CI, 90.9-98.6) comparable to those in the experimental group 89.2% (95% CI 84.1-94.7) and 95.6% (95% CI 91.8-99.6), respectively. Non-inferiority was established as a one-sided 95% upper confidence bound for the difference in probability of 5-year EFS was 0.003, and that for 5-year OS was 0.01 by as-treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3-PBX1 positive ALL.

Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia.

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

Cumulative live birth rates over multiple complete cycles of in vitro fertilisation cycles: 10-year cohort study of 20,687 women following freeze-all strategy from one single centre.

PURPOSE: To explore the cumulative live birth rates (CLBRs) over multiple complete cycles of in vitro fertilization (IVF) among patients following freeze-all strategy METHODS: A retrospective cohort study was performed among 20,687 women undergoing their first and following IVF cycles from 2007 to 2016. The main outcomes of present study were live birth rate per cycle, conservative CLBR and optimal CLBR. RESULTS: The CLBR increased from 50.74% for the first complete cycle to 64.41% for the conservative estimate and 84.77% for the optimal estimate after seven complete cycles. The CLBRs varied by age. The conservative estimate of CLBR after five complete cycles declined from 77.11% for women younger than 31 years, to 8.63% for women older than 40 years. The optimal CLBRs were 91.82% and 13.74%, respectively. The predictors of live birth over multiple complete cycles for patients embarking on IVF following freeze-all strategy were women's age and causes of infertility. For patients finishing the first complete cycle, the number of oocytes retrieved at complete cycle one also played an important predictive role. CONCLUSIONS: Among women undergoing IVF following freeze-all strategy, the CLBR after seven complete IVF cycles was 84.77% if there were not barriers to continue the IVF treatment, with variation by age. Two prediction models were developed to estimate their probability of having a baby over multiple complete IVF cycles with freeze-all strategy among patients before starting IVF and patients after the first complete cycle, which is critical for patients to make treatment decisions and preparations physically, emotionally, and financially.

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

BACKGROUND: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia. METHODS: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m2) plus oral dexamethasone (6 mg/m2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706. FINDINGS: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060). INTERPRETATION: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia. FUNDING: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

YTHDF2 is essential for spermatogenesis and fertility by mediating a wave of transcriptional transition in spermatogenic cells.

The dynamic and reversible regulation roles of m6A modification and the characterization of m6A readers have provided new insights into spermatogenesis at the post-transcriptional level. YTHDF2, as an m6A reader, has been reported to mediate the m6A-containing transcript decay during the mouse oocyte maturation, embryonic stem cell differentiation, neural development, and zebrafish maternal-to-zygotic transition. However, the roles of YTHDF2 in mammalian spermatogenesis are uncertain. Here, we generated germ cell-specific Ythdf2 mutants (Ythdf2-vKO) at a C57BL/6J background and demonstrated that YTHDF2 is essential for mouse spermatogenesis and fertility. Ythdf2-vKO provides oligoasthenoteratozoospermia phenotype with increased apoptosis in germ cells. High-throughput RNA-seq analysis showed that a group of mRNAs is upregulated in Ythdf2-vKO mouse testis; further analysis and MeRIP-qPCR data showed that most of the upregulated genes in Ythdf2-vKO mouse testis are modified with m6A and are YTHDF2 candidate binding genes. Interestingly, RNA-seq analysis combined with our previous single-cell transcriptomics data of mouse spermatogenesis pointed out the failure of a wave of transcript transition during the spermatogenesis of Ythdf2-vKO mice, which was confirmed by gene expression analysis using qPCR of diplotene spermatocytes and round spermatids obtained through fluorescence-activated cell sorting. Our study demonstrates the fundamental role of YTHDF2 during mouse spermatogenesis and provides a potential candidate for the diagnosis of male infertility with the oligoasthenoteratozoospermia syndrome.

Syringin alleviates ovalbumin-induced lung inflammation in BALB/c mice asthma model via NF-κB signaling pathway.

Asthma is an allergic chronic inflammatory disease of the pulmonary airways, characterized by the infiltration of white blood cells and release of inflammatory cytokines of complex pathways linked to its pathogenesis. Syringin extracted from various medicinal plants has been used extensively for the treatment of inflammatory diseases. Hence, this study was conducted to further explore the protective effects of the syringin in ovalbumin (OVA) induced-asthma mice model. OVA-sensitized BALB mice were treated intraperitonealy with three doses (25, 50 and 100 mg/kg) of the syringin which was validated by the alteration in the immunoglobulin E (IgE) levels, cytokines levels, histopathological evaluation inflammatory cell count, lung weight, nitrite (NO) levels, oxidative stress biomarkers and gene markers. The treatment of syringin intensely reduced the increased IgE, inflammatory cytokines, WBC count and restored the antioxidant stress markers OVA stimulated animals. In addition, a significant reduction in inflammation and mucus production was evidenced in histopathological analysis which was further validated by suppression NF-κB pathway activation by syringin. These results suggest that syringin may improve asthma symptoms in OVA-induced mice by modulating NF-κB pathway activation.

The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles.

STUDY QUESTION: To evaluate the impact of storage time after vitrification on embryo viability, pregnancy outcomes and neonatal outcomes. SUMMARY ANSWER: The prolonged storage time of vitrified embryos negatively affected pregnancy outcomes, including biochemical pregnancy rate, clinical pregnancy and live birth rate; but did not influence neonatal outcomes. WHAT IS KNOWN ALREADY: Although vitrification has been the fundamental tool of ART treatments in recent years, few studies have explored the influence of storage period after vitrification on embryonic and clinical outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed among 24 698 patients with the first vitrified embryo transfer following a freeze-all strategy during the period from January 2011 to December 2017. PARTICIPANTS/MATERIAL, SETTING, METHODS: A total of 24 698 patients met the inclusion criteria and were grouped according to the storage time (11 330 patients in Group 1 with storage time <3 months, 9614 patients in Group 2 with storage time between 3 and 6 months, 3188 patients in Group 3 with storage time between 6 and 12 months and 566 in Group 4 with storage time between 12 and 24 months). The pregnancy outcomes and neonatal outcomes were compared between different storage time groups. Multivariate logistic regression and linear regression were performed to evaluate the independent effect of storage time on clinical outcomes, adjusting for important confounders. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for potential confounding factors, the chance of biochemical pregnancy (Group 1 as reference; Group 2: adjusted odds ratio (aOR) = 0.92, 95% CI 0.87-0.97; Group 3: aOR = 0.83, 95% CI 0.76-0.90; Group 4: aOR = 0.68, 95% CI 0.56-0.81), clinical pregnancy (Group 2: aOR = 0.91, 95% CI 0.86-0.96; Group 3: aOR = 0.80, 95% CI 0.73-0.87; Group 4: aOR = 0.65, 95% CI 0.54-0.79) and live birth (Group 2: aOR = 0.89, 95% CI 0.85-0.95; Group 3: aOR = 0.83, 95% CI 0.76-0.91; Group 4: aOR = 0.59, 95% CI 0.48-0.72) significantly decreased with the increasing storage time, whereas the relationship between miscarriage, ectopic pregnancy and storage time did not reach statistical significance. In addition, there was no evidence of differences in adverse neonatal outcomes (preterm birth, low birthweight, high birthweight, macrosomia or birth defects) between groups. LIMITATION, REASONS FOR CAUTION: Our study was limited by the retrospective design from a single center, the conclusion from our study needs to be verified in further studies. WIDER IMPLICATIONS OF THE FINDINGS: This study provides new findings about the relationship between prolonged storage time of vitrified embryos and clinical outcomes and offers evidence for the safety of using long-stored embryos after vitrification. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant nos. 81903324, 81771533, 81571397, 81701523), National Key Research and Development Program of China (grant no. SQ2018YFC100163). None of the authors have any conflicts of interest to declare.

Live birth rate and neonatal outcome following cleavage-stage embryo transfer versus blastocyst transfer using the freeze-all strategy.

RESEARCH QUESTION: What are the live birth rates and neonatal outcomes following cleavage-stage embryo transfer and blastocyst transfer in a freeze-all treatment scenario? DESIGN: This was a retrospective cohort study. All good-quality embryos were frozen on the third day; the remaining embryos were grown on until they reached blastocyst stage and then frozen. Between 2007 and 2016, 11,801 patients underwent cleavage-stage embryo transfer and 1009 patients underwent blastocyst transfer in the first treatment cycle using the freeze-all strategy. The live birth rate and neonatal outcomes were evaluated. RESULTS: The live birth rate in the first frozen embryo transfer cycle was higher following blastocyst transfer than following cleavage-stage transfer (69.1% versus 55.5%, P < 0.01), but there was no difference in live birth rate in the second frozen embryo transfer cycle between blastocyst transfer and cleavage-stage transfer (45.2% versus 52.7%, P > 0.05). Similarly, no difference was found in the cumulative live birth rate for the first complete IVF cycle (71.1% versus 69.2%, P > 0.05). Blastocyst transfer gave a higher risk of preterm singleton delivery than did cleavage-stage transfer. However, there was no difference in the risk of early preterm delivery, low birth weight, very low birth weight, high birth weight and very high birth weight between the two groups. CONCLUSIONS: There is no evidence to support the superiority of blastocyst transfer compared with cleavage-stage transfer in a freeze-all treatment scenario. There may be a higher risk of preterm singleton delivery following blastocyst transfer than following cleavage-stage transfer but further studies are needed to verify this.

Effects of pre-pregnancy body mass index on pregnancy and perinatal outcomes in women with PCOS undergoing frozen embryo transfer.

BACKGROUND: Previous studies have shown that among women with polycystic ovary syndrome who have difficulties conceiving, frozen-embryo transfer resulted in increased live birth rates and decreased ovarian hyperstimulation syndrome risk than did fresh-embryo transfer. In the present retrospective analysis, we sought to determine the effect of body mass index (BMI) on pregnancy and perinatal outcomes in women with PCOS undergoing FET. METHODS: Women with PCOS (n = 1556) undergoing FET were divided into groups based on weight, with those with normal weight having a BMI of 18.5-24.9 kg/m2,those who were overweight having a BMI of 25-29.9 kg/m2, and those who were obese having a BMI ≥30 kg/m2. Both pregnancy and perinatal outcomes were compared among these groups. RESULTS: The normal-weight, overweight, or obese groups exhibited similar pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate and live birth rate. In singletons, birth characteristics regarding newborn gender, gestational age, birthweight and length at birth were comparable between the three groups. For adverse neonatal outcomes, the three groups showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, and very preterm birth after adjustment. In addition, the obstetric complications and the frequencies of live-birth defects were also comparable between the three groups except that overweight and obese women were more likely than women of normal weight to have delivered via cesarean section. CONCLUSION: BMI did not affect the pregnancy or perinatal outcomes in women with PCOS undergoing FET.

Cesarean scar endometriosis: presentation of 198 cases and literature review.

BACKGROUND: Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. METHODS: A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. RESULTS: A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. CONCLUSIONS: The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.

The risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers.

PURPOSE: To explore the risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers. METHODS: A retrospective cohort study was conducted including infants born after fresh and vitrified day 3 embryo transfers and those born after vitrified day 5 or 6 blastocyst transfers from January 2005 through December 2016. The outcome measures included any birth defect, multiple birth defects and 13 individual categories of birth defects. RESULTS: Any birth defect occurred in 1.15% of infants born after fresh day 3 embryo transfers, 1.75% of infants born after vitrified day 3 embryo transfers, 1.60% of infants born after vitrified day 5 blastocyst transfers and 1.10% of infants born after vitrified day 6 blastocyst transfers. There was no difference in the risk of birth defects between vitrified blastocyst-stage transfers and vitrified cleavage-stage transfers (including day 5 vs. day 3 and day 6 vs. day 3) among all births or in only singletons or twins. For infants born after cleavage-stage embryo transfers at day 3, there was no difference in the risk of birth defects between fresh embryo transfers and vitrified embryo transfers among all births or in only singletons or twins. CONCLUSIONS: Transfer of vitrified day 5 or 6 blastocysts does not increase the risk of birth defects compared with vitrified day 3 embryos. However, randomized control trials and follow-up studies of the long-term outcome of children born after blastocyst-stage transfers are needed to confirm the clinical safety of extending embryo culture to the blastocyst stage.

Comprehensive Evaluation of Coal-Fired Power Units Using Grey Relational Analysis and a Hybrid Entropy-Based Weighting Method.

In recent years, coal-fired power plants contribute the biggest part of power generation in China. Challenges of energy conservation and emission reduction of the coal-fired power plant encountering with a rapid growth due to the rising proportion of renewable energy generation in total power generation. Energy saving power generation dispatch (ESPGD) based on power units sorting technology is a promising approach to meet the challenge. Therefore, it is crucial to establish a reasonable and feasible multi-index comprehensive evaluation (MICE) framework for assessing the performance of coal-fired power units accessed by the power grid. In this paper, a hierarchical multiple criteria evaluation system was established. Except for the typical economic and environmental indices, the evaluation system considering operational flexibility and power quality indices either. A hybrid comprehensive evaluation model was proposed to assess the unit operational performance. The model is an integration of grey relational analysis (GRA) with analytic hierarchy process (AHP) and a novel entropy-based method (abbreviate as BECC) which integrates bootstrap method and correlation coefficient (CC) into entropy principle to get the objective weight of indices. Then a case study on seven typical 600 megawatts coal-fired power units was carried out to illustrate the proposed evaluation model, and a weight sensitivity analysis was developed in addition. The results of the case study shows that unit 4 has the power generating priority over the rest ones, and unit 2 ranks last, with the lowest grey relational degree. The weight sensitivity analysis shows that the environmental factor has the biggest sensitivity coefficient. And the validation analysis of the developed BECC weight method shows that it is feasible for the MICE model, and it is stable with an ignorable uncertainty caused by the stochastic factor in the bootstrapping process. The elaborate analysis of the result reveals that it is feasible to rank power units with the proposed evaluation model. Furthermore, it is beneficial to synthesize the updated multiple criteria in optimizing the power generating priority of coal-fired power units.

Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: A retrospective multicenter study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. PROCEDURE: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. RESULTS: The median age at diagnosis was 2.2 years (range, 0-14.6 years), with a peak age of HLH onset at 0 to 3 years (63%). Mutations in HLH-related genes were found in 27.9% (24/86) patients who underwent genetic testing. PRF1, UNC13D, STXBP2 and LYST were the predominant genes involved. Sixteen patients (66.7%) presented with only monoallelic mutations in one gene. Epstein-Barr virus (EBV) infection was the major condition related to HLH, which was documented in 74.4% (201/270) of the patients who underwent EBV detection. Of 252 evaluable patients, 64.7% (163) achieved non-active disease at the eighth week and patients treated with a protocol containing etoposide presented higher remission rates (75.6% vs. 46.8%, P < 0.001). In multivariate analysis, a younger age at diagnosis (<12 months), platelet count less than 80×109 /L, central nervous system involvement, and initial treatment using a protocol without etoposide (not HLH-94/04) were independent prognostic factors indicating resistant disease. DISCUSSION: This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.

Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos.

Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development.