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Abstract Background The APETALA2 (AP2) transcription factor (TF) superfamily, one of the largest gene families in plants, plays an essential role in regulating plant growth and their stress responses. However, the role of AP2 in rice under pesticide stress remains unclear. To investigate the characteristics and functions of the rice AP2 gene family under pesticide stress, the expression of 105 AP2-coding genes and 26 AP2 differentially expressed genes (DEGs) were identified in mesotrione (MTR)-treated rice transcriptome datasets. Results Three subfamilies of the AP2 gene family (AP2/ERF, RAV, and soloists) were identified using sequence alignment and phylogenetic analysis. Chromosome location analysis revealed that the 26 rice AP2 DEGs were unevenly distributed on 10 of the 12 rice chromosomes, and segmental duplication contributed to the expansion of Oryza sativa AP2 (OsAP2) gene family. Collinearity analyses demonstrated that rice AP2 genes displayed 16 orthologous gene pairs, and 12 and 26 orthologous gene pairs were shared of Arabidopsis and soybean, respectively. In addition, rice AP2 genes featured various gene structures, cis-elements, motif compositions, and conserved domains that allowed them to encode genes that elicit biotic and abiotic stress responses. An analysis of docking between MTR and six AP2 DEGs revealed amino acid residues involved in MTR binding. Quantitative reverse transcription–polymerase chain reaction verified that several AP2 genes were preferentially expressed during MTR-induced stress. The roles of OsAP2 proteins in MTR metabolism were further supported by protein–protein interaction network analysis, which illustrated how these proteins interact with target proteins. Conclusion The initial findings of this study define the features of the OsAP2 superfamily and offer important tools for functional analyses of OsAP2 genes implicated in the metabolism of MTR. Graphical Abstract

Abstract Background This study explores and analyzes the clinical characteristics and prognostic factors of hepatoblastoma (HB) in children under 6 years old and establishes a new risk-stratification system for individualized therapy. Methods The clinical data of 382 pediatric patients under 6 years old (231 males and 151 females) who had been diagnosed with HB by pathology between May 2005 and May 2019 were collected. By analyzing the risk factors influencing the survival rate of patients with HB, a new risk-stratification system was established, and it was compared with previous risk-stratification systems by a receiver operating characteristic (ROC) curve. Results (1) According to a Kaplan-Meier survival analysis, the one-year, three-year, and five-year overall survival (OS) was 93.7, 84.0, and 73.9%, respectively, and the event-free survival (EFS) was 90.5, 79.2, and 67.5%, respectively. (2) The independent risk factors influencing prognosis in pediatric patients with HB were alpha-fetoprotein (AFP) 1000 ng/ml (HR = 3.341, P = 0.005); platelet count > 400 × 109/L (pooled hazard ratio [HR] = 2.123, P = 0.026); PRETEXT stage IV (HR = 4.026, P = 0.001); vascular involvement (HR = 2.178, P = 0.019); distant metastasis (HR = 2.634, P = 0.010);and multifocality (HR = 2.215, P = 0.012). (3) A new risk-stratification system was established and divided into three groups: low risk, moderate risk, and high risk. There were statistical differences among the three groups (P = 0.002). Compared with the previous risk-staging systems, there was no significant difference in the survival rate. Although the effect in the guiding therapy was the same, the area under the curve for the ROC curve was 0.835 (95% CI: 0.784–0.885) for the new stratification system. Conclusion This new risk-stratification system had a better predictive value for the prognosis of pediatric patients with HB than other stratification systems.

Abstract Background To analyze the clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma (RB) and intracranial segment of retrobulbar optic nerve invasion. Methods A total of 14 children with unilateral RB and intracranial segment of retrobulbar optic nerve invasion were enrolled in this retrospective study from January 2009 to December 2018. Clinical characteristics, treatment and prognosis were collected and analyzed. Survival curves were calculated by Kaplan-Meier method. Results Of 14 cases, there were 7 male and 7 female, ranging in age from 22.85 to 121.97 months (median, 41.03 months). Seventy-one percent of patients came from first-tier cities in China and effected in the left eye. Magnetic resonance imaging (MRI) results indicated that all patients presented with thickened and enhanced optic nerve and intracranial segment of optic nerve invasion. Nine patients received comprehensive therapeutic regimen (chemotherapy, eye enucleation, radiotherapy and intrathecal therapy). The patients were followed up to December 2019, with a median follow-up of 20.6 months. The median disease specific survival was 48.99 ± 8.62 months, and the overall survival (OS) rate was 64.3%. Radiotherapy and comprehensive therapeutic regimen had significant impact on survival time (all p

ObjectiveTo evaluate the pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocol for patients with endometrioma underwent in vitro fertilization/intra-cytoplasmic sperm injection embryo transfer (IVF/ICSI-ET).DesignObservational retrospective cohort study.SettingUniversity affiliated reproductive center.Study Participants605 infertile patients with endometrioma underwent IVF/ICSI-ET from January 2016 to March 2021 were included in this study.MethodsMultivariable logistic regression analyses were conducted to determine the independent effect of controlled ovarian stimulation (COS) protocols on reproductive outcomes of first embryo transfer (ET) cycles. The live birth was primary outcome, the implantation rate, biochemical pregnancy, clinical pregnancy and ongoing pregnancy were secondary outcomes.ResultsCompared to PPOS protocol, the probability of implantation showed no significant difference with ultra-long gonadotrophin-releasing hormone agonist (GnRHa) protocol and gonadotrophin-releasing hormone antagonist (GnRHant) protocol (OR 1.7, 95% CI 0.9-3.1, OR 1.2, 95% CI 0.7-2.1, respectively). The PPOS protocol was correlated with a significantly lower biochemical pregnancy and clinical pregnancy than ultra-long GnRHa protocol in the multivariable logistic regression analysis (OR 2.3, 95% CI 1.1-4.9, OR 2.4, 95% CI 1.1-5.3, respectively). However, there was no significant difference in terms of biochemical pregnancy, clinical pregnancy and ongoing pregnancy between PPOS and GnRHant protocol (OR 1.4, 95% CI 0.7-2.7, OR 1.3, 95% CI 0.7-2.4, OR 1.1, 95% CI 0.6-2.3, respectively). In addition, compared to PPOS protocol, ultra-long GnRHa protocol and GnRHant protocol demonstrated no statistical difference in ongoing pregnancy (OR 2.0, 95% CI 0.9-4.5, OR 2.1, 95% CI 0.6-2.3, respectively). Notably, the ultra-long GnRHa protocol was associated with a significant higher probability of live birth than PPOS protocol both in crude analysis and multivariable logistic regression analysis (OR 2.6, 95% CI 1.3-5.1, OR 2.5, 95% CI 1.1-5.7, respectively). Nevertheless, no statistical difference was found in live birth between PPOS and GnRHant protocol either in crude analysis and multivariable logistic regression analysis (OR1.2, 95% CI 0.6-2.3, OR 1.2, 95% CI 0.6-2.5, respectively).ConclusionsBased on the reproductive outcomes of the first ET cycles in patients with endometrioma, PPOS protocol may associated with inferior reproductive outcomes in terms of biochemical pregnancy, clinical pregnancy and live birth than ultra-long GnRHa protocol. However, there was no significant difference in implantation rate, clinical pregnancy, ongoing pregnancy and live birth between PPOS and GnRHant protocol.

A message passing interface (MPI) parallel scheme on distributed memory platforms is developed for the low-rank decomposition to accommodate the memory requirement during angular sweeping of a rough surface in terms of tapered wave incidence. Numerical examples, including that conducted on a 160 × 160 square wavelength rough surface, are carried out to demonstrate the performance of the proposed MPI angular sweeping with respect to accuracy, efficiency, scalability, and the peak memory requirement.

Objective To assess the awareness, attitude and barriers of colorectal cancer screening among high-risk populations in China.Design A cross-sectional study was employed.Setting This study was conducted in nine hospitals in Hunan province, China.Participants Individuals with a high-risk for colorectal cancer were interviewed using a pretested structured questionnaire.Primary and secondary outcome measures Knowledge, attitude towards colorectal cancer screening, sociodemographic factors associated with screening knowledge and behaviour and barriers of colorectal cancer screening.Results This study included 684 participants. The mean knowledge score was 11.86/24 (SD 4.84). But over 70% of them held a positive attitude towards screening. Only 13.3% had undergone colorectal cancer screening. Independent factors related to knowledge were education level of college or above, working as a white collar, higher income, having health insurance, having seen a doctor in the past year and with a high perceived risk (p

BackgroundThe risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle.MethodsA systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity.ResultsAmong 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [0.29, 0.44], MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR = 0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]).ConclusionHigh BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.

Abstract Introduction To identify possible prognostic factors in children with head and neck rhabdomyosarcoma (RMS). Methods A total of 98 patients with head and neck RMS were enrolled in this retrospective study from February 2005 to September 2017. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. Survival curves were calculated by Kaplan–Meier method. Results At the study closing date, there were 60 patients alive, 37 patients died, one patient was lost to follow‐up, and 47 patients relapsed. The median disease‐specific survival was 60.00 ± 25.36 months, and the overall survival (OS) rate was 61.9%. Complete remission was associated with a longer disease‐specific survival (86.6%) compared with partial remission (6.7%). In addition, patients with age >3 years had better OS rate (69.0%) compared with age ≤3 years (42.3%). Univariate and multivariate analysis showed that chemotherapy efficacy and age were prognostic factors of disease‐specific survival. Conclusions Improvement in outcome was obtained with comprehensive treatment for head and neck RMS. Both chemotherapy efficacy and age of patients were prognostic factors for children with head and neck RMS, which provide some valuable information for further treatment.

Background Management guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes. Methods We retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis. Results The male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3–62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P=0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival. Conclusion The rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy. [ABSTRACT FROM AUTHOR]

Letter to the editor

The aim of the present study was to assess the toxicity and efficacy of autologous peripheral blood stem cell (APBSC) transplantation in children with advanced malignant solid tumors. The outcomes of 38 children with advanced malignant solid tumor, who were treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation in Beijing Tongren Hospital (Capital Medical University, Beijing, China) between September 2005 and November 2011, were retrospectively analyzed. The effects of treatment were evaluated according to the standard Bearman's criteria. The mean count of collected mononuclear cells and the cluster of differentiation 34+ cell count from 38 patients was 5.6±2.2x108/kg and 3.8±2.6x106/kg, respectively. From these 38 patients, the number of stem cells collected from 31 cases (81.6%) accorded with the transplantation standards. Three and 14 days after pretreatment in these 38 cases, there were 19 cases of grade I, 11 cases of grade II, five cases of grade III and three cases of grade IV (one case succumbed) adverse reaction. Following the treatment (23-40 days after pretreatment, during organ injury recovery), 37 cases obtained bone marrow reconstitution with a mean time of 12.3±3.1 days after APBSC reinfusion. The median survival time of the 37 patients was 49 months, and the survival rate at one, three and five years post-treatment was 91.9, 68.2 and 36.6%, respectively. [ABSTRACT FROM AUTHOR]

TLR/IL-1R signaling plays a critical role in sensing various harmful foreign pathogens and mounting efficient innate and adaptive immune responses, and it is tightly controlled by intracellular regulators at multiple levels. In particular, TOLLIP forms a constitutive complex with IRAK1 and sequesters it in the cytosol to maintain the kinase in an inactive conformation under unstimulated conditions. However, the underlying mechanisms by which IRAK1 dissociates from TOLLIP to activate TLR/IL-1R signaling remain obscure. Herein, we show that BLK positively regulates TLR/IL-1R-mediated inflammatory response. BLKdeficient mice produce less inflammatory cytokines and are more resistant to death upon IL-1β challenge. Mechanistically, BLK is preassociated with IL1R1 and IL1RAcP in resting cells. IL-1β stimulation induces heterodimerization of IL1R1 and IL1RAcP, which further triggers BLK autophosphorylation at Y309. Activated BLK directly phosphorylates TOLLIP at Y76/86/152 and further promotes TOLLIP dissociation from IRAK1, thereby facilitating TLR/IL-1R-mediated signal transduction. Overall, these findings highlight the importance of BLK as an active regulatory component in TLR/IL-1R signaling. [ABSTRACT FROM AUTHOR]

Abstract Background Evidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China. Methods We included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL. Results After a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41–59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029–12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475–2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623–3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941–4.892) were independent risk factors for survival (p

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.